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Journal articles on the topic 'Centromer'
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1
Kapoor, Shivali, Lisha Zhu, Cara Froyd, Tao Liu, and Laura N. Rusche. "Regional centromeres in the yeastCandida lusitaniaelack pericentromeric heterochromatin." Proceedings of the National Academy of Sciences 112, no. 39 (September 14, 2015): 12139–44. http://dx.doi.org/10.1073/pnas.1508749112.
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Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeastCandida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4–4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin inC. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and aURA3reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.
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Batzenschlager, Morgane, Inna Lermontova, Veit Schubert, Jörg Fuchs, Alexandre Berr, Maria A. Koini, Guy Houlné, et al. "Arabidopsis MZT1 homologs GIP1 and GIP2 are essential for centromere architecture." Proceedings of the National Academy of Sciences 112, no. 28 (June 29, 2015): 8656–60. http://dx.doi.org/10.1073/pnas.1506351112.
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Centromeres play a pivotal role in maintaining genome integrity by facilitating the recruitment of kinetochore and sister-chromatid cohesion proteins, both required for correct chromosome segregation. Centromeres are epigenetically specified by the presence of the histone H3 variant (CENH3). In this study, we investigate the role of the highly conserved γ-tubulin complex protein 3-interacting proteins (GIPs) in Arabidopsis centromere regulation. We show that GIPs form a complex with CENH3 in cycling cells. GIP depletion in the gip1gip2 knockdown mutant leads to a decreased CENH3 level at centromeres, despite a higher level of Mis18BP1/KNL2 present at both centromeric and ectopic sites. We thus postulate that GIPs are required to ensure CENH3 deposition and/or maintenance at centromeres. In addition, the recruitment at the centromere of other proteins such as the CENP-C kinetochore component and the cohesin subunit SMC3 is impaired in gip1gip2. These defects in centromere architecture result in aneuploidy due to severely altered centromeric cohesion. Altogether, we ascribe a central function to GIPs for the proper recruitment and/or stabilization of centromeric proteins essential in the specification of the centromere identity, as well as for centromeric cohesion in somatic cells.
3
Liang, Cai, Zhenlei Zhang, Qinfu Chen, Haiyan Yan, Miao Zhang, Xingfeng Xiang, Qi Yi, Xuan Pan, Hankun Cheng, and Fangwei Wang. "A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells." Journal of Biological Chemistry 294, no. 5 (November 29, 2018): 1437–50. http://dx.doi.org/10.1074/jbc.ra118.006046.
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The inner centromere region of a mitotic chromosome critically regulates sister chromatid cohesion and kinetochore–microtubule attachments. However, the molecular mechanism underlying inner centromere assembly remains elusive. Here, using CRISPR/Cas9-based gene editing in HeLa cells, we disrupted the interaction of Shugoshin 1 (Sgo1) with histone H2A phosphorylated on Thr-120 (H2ApT120) to selectively release Sgo1 from mitotic centromeres. Interestingly, cells expressing the H2ApT120-binding defective mutant of Sgo1 have an elevated rate of chromosome missegregation accompanied by weakened centromeric cohesion and decreased centromere accumulation of the chromosomal passenger complex (CPC), an integral part of the inner centromere and a key player in the correction of erroneous kinetochore–microtubule attachments. When artificially tethered to centromeres, a Sgo1 mutant defective in binding protein phosphatase 2A (PP2A) is not able to support proper centromeric cohesion and CPC accumulation, indicating that the Sgo1–PP2A interaction is essential for the integrity of mitotic centromeres. We further provide evidence indicating that Sgo1 protects centromeric cohesin to create a binding site for the histone H3–associated protein kinase Haspin, which not only inhibits the cohesin release factor Wapl and thereby strengthens centromeric cohesion but also phosphorylates histone H3 at Thr-3 to position CPC at inner centromeres. Taken together, our findings reveal a positive feedback–based mechanism that ensures proper assembly of the functional inner centromere during mitosis. They further suggest a causal link between centromeric cohesion defects and chromosomal instability in cancer cells.
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Jaco, Isabel, Andrés Canela, Elsa Vera, and Maria A. Blasco. "Centromere mitotic recombination in mammalian cells." Journal of Cell Biology 181, no. 6 (June 9, 2008): 885–92. http://dx.doi.org/10.1083/jcb.200803042.
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Centromeres are special structures of eukaryotic chromosomes that hold sister chromatid together and ensure proper chromosome segregation during cell division. Centromeres consist of repeated sequences, which have hindered the study of centromere mitotic recombination and its consequences for centromeric function. We use a chromosome orientation fluorescence in situ hybridization technique to visualize and quantify recombination events at mouse centromeres. We show that centromere mitotic recombination occurs in normal cells to a higher frequency than telomere recombination and to a much higher frequency than chromosome-arm recombination. Furthermore, we show that centromere mitotic recombination is increased in cells lacking the Dnmt3a and Dnmt3b DNA methyltransferases, suggesting that the epigenetic state of centromeric heterochromatin controls recombination events at these regions. Increased centromere recombination in Dnmt3a,3b-deficient cells is accompanied by changes in the length of centromere repeats, suggesting that prevention of illicit centromere recombination is important to maintain centromere integrity in the mouse.
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Morency, Eric, Mirna Sabra, Frédéric Catez, Pascale Texier, and Patrick Lomonte. "A novel cell response triggered by interphase centromere structural instability." Journal of Cell Biology 177, no. 5 (June 4, 2007): 757–68. http://dx.doi.org/10.1083/jcb.200612107.
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Interphase centromeres are crucial domains for the proper assembly of kinetochores at the onset of mitosis. However, it is not known whether the centromere structure is under tight control during interphase. This study uses the peculiar property of the infected cell protein 0 of herpes simplex virus type 1 to induce centromeric structural damage, revealing a novel cell response triggered by centromere destabilization. It involves centromeric accumulation of the Cajal body–associated coilin and fibrillarin as well as the survival motor neuron proteins. The response, which we have termed interphase centromere damage response (iCDR), was observed in all tested human and mouse cells, indicative of a conserved mechanism. Knockdown cells for several constitutive centromere proteins have shown that the loss of centromeric protein B provokes the centromeric accumulation of coilin. We propose that the iCDR is part of a novel safeguard mechanism that is dedicated to maintaining interphase centromeres compatible with the correct assembly of kinetochores, microtubule binding, and completion of mitosis.
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Ávila Robledillo, Laura, Pavel Neumann, Andrea Koblížková, Petr Novák, Iva Vrbová, and Jiří Macas. "Extraordinary Sequence Diversity and Promiscuity of Centromeric Satellites in the Legume Tribe Fabeae." Molecular Biology and Evolution 37, no. 8 (April 7, 2020): 2341–56. http://dx.doi.org/10.1093/molbev/msaa090.
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Abstract Satellite repeats are major sequence constituents of centromeres in many plant and animal species. Within a species, a single family of satellite sequences typically occupies centromeres of all chromosomes and is absent from other parts of the genome. Due to their common origin, sequence similarities exist among the centromere-specific satellites in related species. Here, we report a remarkably different pattern of centromere evolution in the plant tribe Fabeae, which includes genera Pisum, Lathyrus, Vicia, and Lens. By immunoprecipitation of centromeric chromatin with CENH3 antibodies, we identified and characterized a large and diverse set of 64 families of centromeric satellites in 14 species. These families differed in their nucleotide sequence, monomer length (33–2,979 bp), and abundance in individual species. Most families were species-specific, and most species possessed multiple (2–12) satellites in their centromeres. Some of the repeats that were shared by several species exhibited promiscuous patterns of centromere association, being located within CENH3 chromatin in some species, but apart from the centromeres in others. Moreover, FISH experiments revealed that the same family could assume centromeric and noncentromeric positions even within a single species. Taken together, these findings suggest that Fabeae centromeres are not shaped by the coevolution of a single centromeric satellite with its interacting CENH3 proteins, as proposed by the centromere drive model. This conclusion is also supported by the absence of pervasive adaptive evolution of CENH3 sequences retrieved from Fabeae species.
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Sullivan, Beth, and Gary Karpen. "Centromere identity in Drosophila is not determined in vivo by replication timing." Journal of Cell Biology 154, no. 4 (August 20, 2001): 683–90. http://dx.doi.org/10.1083/jcb.200103001.
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Centromeric chromatin is uniquely marked by the centromere-specific histone CENP-A. For assembly of CENP-A into nucleosomes to occur without competition from H3 deposition, it was proposed that centromeres are among the first or last sequences to be replicated. In this study, centromere replication in Drosophila was studied in cell lines and in larval tissues that contain minichromosomes that have structurally defined centromeres. Two different nucleotide incorporation methods were used to evaluate replication timing of chromatin containing CID, a Drosophila homologue of CENP-A. Centromeres in Drosophila cell lines were replicated throughout S phase but primarily in mid S phase. However, endogenous centromeres and X-derived minichromosome centromeres in vivo were replicated asynchronously in mid to late S phase. Minichromosomes with structurally intact centromeres were replicated in late S phase, and those in which centric and surrounding heterochromatin were partially or fully deleted were replicated earlier in mid S phase. We provide the first in vivo evidence that centromeric chromatin is replicated at different times in S phase. These studies indicate that incorporation of CID/CENP-A into newly duplicated centromeres is independent of replication timing and argue against determination of centromere identity by temporal sequestration of centromeric chromatin replication relative to bulk genomic chromatin.
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Okada, Masahiro, Katsuya Okawa, Toshiaki Isobe, and Tatsuo Fukagawa. "CENP-H–containing Complex Facilitates Centromere Deposition of CENP-A in Cooperation with FACT and CHD1." Molecular Biology of the Cell 20, no. 18 (September 15, 2009): 3986–95. http://dx.doi.org/10.1091/mbc.e09-01-0065.
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Centromere identity is thought to be determined by epigenetic mechanisms. The centromere-specific histone H3 variant CENP-A plays a central role in specifying the locus where the centromere is constructed. However, the precise mechanisms that target CENP-A to centromeric chromatin are poorly understood. Here, we show that facilitates chromatin transcription (FACT) localizes to centromeres in a CENP-H–containing complex-dependent manner. In conditional mutant cell lines for SSRP1, a subunit of FACT, centromere targeting of newly synthesized CENP-A is severely inhibited. The chromatin remodeling factor CHD1 binds to SSRP1 both in vivo and in vitro and associates with centromeres. The centromeric localization of CHD1 is lost in SSRP1-depleted cells. RNA interference knockdown of CHD1 leads to a decrease in the amount of centromere localized CENP-A. These findings indicate that the CENP-H–containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1.
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Dalal, Yamini. "Epigenetic specification of centromeresThis paper is one of a selection of papers published in this Special Issue, entitled 29th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process." Biochemistry and Cell Biology 87, no. 1 (February 2009): 273–82. http://dx.doi.org/10.1139/o08-135.
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Centromeres are the discrete sites of spindle microtubule attachment on chromosomes during mitosis and meiosis in all eukaryotes. These highly specialized chromatin structures typically occupy the same site for thousands of generations, yet the mechanism by which centromeres are established, maintained, and function remain a mystery. In metazoans, centromeric DNA sequence has proven not to be the key determinant of centromeric identity; therefore, centromeres are thought to be epigenetically specified by their specialized chromatin structure. In all eukaryotes, the centromere-specific histone H3 variant CenH3 replaces canonical H3 within nucleosomes at centric chromatin. This specialized nucleosome is the building block upon which all other centromere-associated proteins depend. This review highlights exciting new findings that have resulted in a paradigm shift in our understanding of CenH3 assembly into centromeric chromatin, CenH3 nucleosomal structure, CenH3 chromatin folding, the contribution of these factors to centromeric identity, and finally, the intimate role cell-cycle-regulated transcription and pericentric heterochromatin play in the maintenance and integrity of centromeres.
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Liu, Yalin, Handong Su, Junling Pang, Zhi Gao, Xiu-Jie Wang, James A. Birchler, and Fangpu Han. "Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize." Proceedings of the National Academy of Sciences 112, no. 11 (March 2, 2015): E1263—E1271. http://dx.doi.org/10.1073/pnas.1418248112.
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The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity.
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Diner, Rachel E., Chari M. Noddings, Nathan C. Lian, Anthony K. Kang, Jeffrey B. McQuaid, Jelena Jablanovic, Josh L. Espinoza, et al. "Diatom centromeres suggest a mechanism for nuclear DNA acquisition." Proceedings of the National Academy of Sciences 114, no. 29 (July 3, 2017): E6015—E6024. http://dx.doi.org/10.1073/pnas.1700764114.
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Centromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum. We observed 25 unique centromere sequences typically occurring once per chromosome, a finding that helps to resolve nuclear genome organization and indicates monocentric regional centromeres. Diatom centromere sequences contain low-GC content regions but lack repeats or other conserved sequence features. Native and foreign sequences with similar GC content to P. tricornutum centromeres can maintain episomes and recruit the diatom centromeric histone protein CENH3, suggesting nonnative sequences can also function as diatom centromeres. Thus, simple sequence requirements may enable DNA from foreign sources to persist in the nucleus as extrachromosomal episomes, revealing a potential mechanism for organellar and foreign DNA acquisition.
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Arunkumar, Ganesan, and Daniël P. Melters. "Centromeric Transcription: A Conserved Swiss-Army Knife." Genes 11, no. 8 (August 9, 2020): 911. http://dx.doi.org/10.3390/genes11080911.
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In most species, the centromere is comprised of repetitive DNA sequences, which rapidly evolve. Paradoxically, centromeres fulfill an essential function during mitosis, as they are the chromosomal sites wherein, through the kinetochore, the mitotic spindles bind. It is now generally accepted that centromeres are transcribed, and that such transcription is associated with a broad range of functions. More than a decade of work on this topic has shown that centromeric transcripts are found across the eukaryotic tree and associate with heterochromatin formation, chromatin structure, kinetochore structure, centromeric protein loading, and inner centromere signaling. In this review, we discuss the conservation of small and long non-coding centromeric RNAs, their associations with various centromeric functions, and their potential roles in disease.
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Ishikura, Shuhei, Kazuhiko Nakabayashi, Masayoshi Nagai, Toshiyuki Tsunoda, and Senji Shirasawa. "ZFAT binds to centromeres to control noncoding RNA transcription through the KAT2B–H4K8ac–BRD4 axis." Nucleic Acids Research 48, no. 19 (September 30, 2020): 10848–66. http://dx.doi.org/10.1093/nar/gkaa815.
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Abstract Centromeres are genomic regions essential for faithful chromosome segregation. Transcription of noncoding RNA (ncRNA) at centromeres is important for their formation and functions. Here, we report the molecular mechanism by which the transcriptional regulator ZFAT controls the centromeric ncRNA transcription in human and mouse cells. Chromatin immunoprecipitation with high-throughput sequencing analysis shows that ZFAT binds to centromere regions at every chromosome. We find a specific 8-bp DNA sequence for the ZFAT-binding motif that is highly conserved and widely distributed at whole centromere regions of every chromosome. Overexpression of ZFAT increases the centromeric ncRNA levels at specific chromosomes, whereas its silencing reduces them, indicating crucial roles of ZFAT in centromeric transcription. Overexpression of ZFAT increases the centromeric levels of both the histone acetyltransferase KAT2B and the acetylation at the lysine 8 in histone H4 (H4K8ac). siRNA-mediated knockdown of KAT2B inhibits the overexpressed ZFAT-induced increase in centromeric H4K8ac levels, suggesting that ZFAT recruits KAT2B to centromeres to induce H4K8ac. Furthermore, overexpressed ZFAT recruits the bromodomain-containing protein BRD4 to centromeres through KAT2B-mediated H4K8ac, leading to RNA polymerase II-dependent ncRNA transcription. Thus, ZFAT binds to centromeres to control ncRNA transcription through the KAT2B–H4K8ac–BRD4 axis.
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Marques, André, Tiago Ribeiro, Pavel Neumann, Jiří Macas, Petr Novák, Veit Schubert, Marco Pellino, et al. "Holocentromeres in Rhynchospora are associated with genome-wide centromere-specific repeat arrays interspersed among euchromatin." Proceedings of the National Academy of Sciences 112, no. 44 (October 21, 2015): 13633–38. http://dx.doi.org/10.1073/pnas.1512255112.
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Holocentric chromosomes lack a primary constriction, in contrast to monocentrics. They form kinetochores distributed along almost the entire poleward surface of the chromatids, to which spindle fibers attach. No centromere-specific DNA sequence has been found for any holocentric organism studied so far. It was proposed that centromeric repeats, typical for many monocentric species, could not occur in holocentrics, most likely because of differences in the centromere organization. Here we show that the holokinetic centromeres of the Cyperaceae Rhynchospora pubera are highly enriched by a centromeric histone H3 variant-interacting centromere-specific satellite family designated “Tyba” and by centromeric retrotransposons (i.e., CRRh) occurring as genome-wide interspersed arrays. Centromeric arrays vary in length from 3 to 16 kb and are intermingled with gene-coding sequences and transposable elements. We show that holocentromeres of metaphase chromosomes are composed of multiple centromeric units rather than possessing a diffuse organization, thus favoring the polycentric model. A cell-cycle–dependent shuffling of multiple centromeric units results in the formation of functional (poly)centromeres during mitosis. The genome-wide distribution of centromeric repeat arrays interspersing the euchromatin provides a previously unidentified type of centromeric chromatin organization among eukaryotes. Thus, different types of holocentromeres exist in different species, namely with and without centromeric repetitive sequences.
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Moore, Landon L., and Mark B. Roth. "Hcp-4, a Cenp-C–Like Protein inCaenorhabditis elegans, Is Required for Resolution of Sister Centromeres." Journal of Cell Biology 153, no. 6 (June 4, 2001): 1199–208. http://dx.doi.org/10.1083/jcb.153.6.1199.
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The centromere plays a critical role in the segregation of chromosomes during mitosis. In mammals, sister centromeres are resolved from one another in the G2 phase of the cell cycle. During prophase, chromosomes condense with sister centromeres oriented in a back to back configuration enabling only one chromatid to be captured by each half spindle. To study this process, we identified a centromere protein (CENP)-C–like protein, holocentric protein (HCP)-4, in Caenorhabditis elegans based on sequence identity, loss of function phenotype, and centromeric localization. HCP-4 is found in the cytoplasm during interphase, but is nuclear localized in mitosis, where it localizes specifically to the centromere. The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F–like protein, HCP-1, indicating an ordered assembly pathway. Loss of HCP-4 expression by RNA-mediated interference resulted in a failure to generate resolution of sister centromeres on chromosomes, suggesting that HCP-4 is required for sister centromere resolution. These chromosomes also failed to form a functional kinetochore. Thus, the CENP-C–like protein HCP-4 is essential for both resolution sister centromeres and attachment to the mitotic spindle.
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Edwards, Nathaniel S., and Andrew W. Murray. "Identification of Xenopus CENP-A and an Associated Centromeric DNA Repeat." Molecular Biology of the Cell 16, no. 4 (April 2005): 1800–1810. http://dx.doi.org/10.1091/mbc.e04-09-0788.
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Kinetochores are the proteinaceous complexes that assemble on centromeric DNA and direct eukaryotic chromosome segregation. The mechanisms by which higher eukaryotic cells define centromeres are poorly understood. Possible molecular contributors to centromere specification include the underlying DNA sequences and epigenetic factors such as binding of the centromeric histone centromere protein A (CENP-A). Frog egg extracts are an attractive system for studying centromere definition and kinetochore assembly. To facilitate such studies, we cloned a Xenopus laevis homologue of CENP-A (XCENP-A). We identified centromere-associated DNA sequences by cloning fragments of DNA that copurified with XCENP-A by chromatin immunoprecipitation. XCENP-A associates with frog centromeric repeat 1 (Fcr1), a 174-base pair repeat containing a possible CENP-B box. Southern blots of partially digested genomic DNA revealed large ordered arrays of Fcr1 in the genome. Fluorescent in situ hybridization with Fcr1 probes stained most centromeres in cultured cells. By staining lampbrush chromosomes, we specifically identified the 11 (of 18) chromosomes that stain consistently with Fcr1 probes.
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Malik, H. S., and J. J. Bayes. "Genetic conflicts during meiosis and the evolutionary origins of centromere complexity." Biochemical Society Transactions 34, no. 4 (July 21, 2006): 569–73. http://dx.doi.org/10.1042/bst0340569.
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Centromeric DNA evolves rapidly, ranging in size and complexity over several orders of magnitude. Traditional attempts at studying centromeres have left unexplained the causes underlying this complexity and rapid evolution. Instead of directly studying centromeric DNA sequence, our approach has been to study the proteins that epigenetically determine centromere identity. We have discovered that centromeric histones (CenH3s) have evolved under positive selection in multiple lineages, suggesting an involvement in recurrent genetic conflict. Our hypothesis is that ‘centromere-drive’ is the source of this conflict. Under this model, centromeres compete via microtubule attachments for preferential transmission in female meioses occurring in animals and plants. Since only one of four meiotic products will become the egg, this competition confers a selfish advantage to chromosomes that can make more microtubule attachments, resulting in runaway expansions of centromeric satellites. While beneficial to the ‘driving’ chromosome, these expansions can have deleterious effects on the fitness of an organism and of the species. CenH3s as well as other heterochromatin proteins have evolved under positive selection to suppress the deleterious consequences of ‘centromere-drive’ by restoring meiotic parity.
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Miller, Joseph T., Fenggao Dong, Scott A. Jackson, Junqi Song, and Jiming Jiang. "Retrotransposon-Related DNA Sequences in the Centromeres of Grass Chromosomes." Genetics 150, no. 4 (December 1, 1998): 1615–23. http://dx.doi.org/10.1093/genetics/150.4.1615.
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Abstract Several distinct DNA fragments were subcloned from a sorghum (Sorghum bicolor) bacterial artificial chromosome clone 13I16 that was derived from a centromere. Three fragments showed significant sequence identity to either Ty3/gypsy- or Ty1/copia-like retrotransposons. Fluorescence in situ hybridization (FISH) analysis revealed that the Ty1/copia-related DNA sequences are not specific to the centromeric regions. However, the Ty3/gypsy-related sequences were present exclusively in the centromeres of all sorghum chromosomes. FISH and gel-blot hybridization showed that these sequences are also conserved in the centromeric regions of all species within Gramineae. Thus, we report a new retrotransposon that is conserved in specific chromosomal regions of distantly related eukaryotic species. We propose that the Ty3/gypsy-like retrotransposons in the grass centromeres may be ancient insertions and are likely to have been amplified during centromere evolution. The possible role of centromeric retrotransposons in plant centromere function is discussed.
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Hartley, Gabrielle A., Mariam Okhovat, Rachel J. O’Neill, and Lucia Carbone. "Comparative Analyses of Gibbon Centromeres Reveal Dynamic Genus-Specific Shifts in Repeat Composition." Molecular Biology and Evolution 38, no. 9 (May 13, 2021): 3972–92. http://dx.doi.org/10.1093/molbev/msab148.
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Abstract Centromeres are functionally conserved chromosomal loci essential for proper chromosome segregation during cell division, yet they show high sequence diversity across species. Despite their variation, a near universal feature of centromeres is the presence of repetitive sequences, such as DNA satellites and transposable elements (TEs). Because of their rapidly evolving karyotypes, gibbons represent a compelling model to investigate divergence of functional centromere sequences across short evolutionary timescales. In this study, we use ChIP-seq, RNA-seq, and fluorescence in situ hybridization to comprehensively investigate the centromeric repeat content of the four extant gibbon genera (Hoolock, Hylobates, Nomascus, and Siamang). In all gibbon genera, we find that CENP-A nucleosomes and the DNA-proteins that interface with the inner kinetochore preferentially bind retroelements of broad classes rather than satellite DNA. A previously identified gibbon-specific composite retrotransposon, LAVA, known to be expanded within the centromere regions of one gibbon genus (Hoolock), displays centromere- and species-specific sequence differences, potentially as a result of its co-option to a centromeric function. When dissecting centromere satellite composition, we discovered the presence of the retroelement-derived macrosatellite SST1 in multiple centromeres of Hoolock, whereas alpha-satellites represent the predominate satellite in the other genera, further suggesting an independent evolutionary trajectory for Hoolock centromeres. Finally, using de novo assembly of centromere sequences, we determined that transcripts originating from gibbon centromeres recapitulate the species-specific TE composition. Combined, our data reveal dynamic shifts in the repeat content that define gibbon centromeres and coincide with the extensive karyotypic diversity within this lineage.
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Baum, M., V. K. Ngan, and L. Clarke. "The centromeric K-type repeat and the central core are together sufficient to establish a functional Schizosaccharomyces pombe centromere." Molecular Biology of the Cell 5, no. 7 (July 1994): 747–61. http://dx.doi.org/10.1091/mbc.5.7.747.
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The DNA requirements for centromere function in fission yeast have been investigated using a minichromosome assay system. Critical elements of Schizosaccharomyces pombe centromeric DNA are portions of the centromeric central core and sequences within a 2.1-kilobase segment found on all three chromosomes as part of the K-type (K/K"/dg) centromeric repeat. The S. pombe centromeric central core contains DNA sequences that appear functionally redundant, and the inverted repeat motif that flanks the central core in all native fission yeast centromeres is not essential for centromere function in circular minichromosomes. Tandem copies of centromeric repeat K", in conjunction with the central core, exert an additive effect on centromere function, increasing minichromosome mitotic stability with each additional copy. Centromeric repeats B and L, however, and parts of the central core and its core-associated repeat are dispensable and cannot substitute for K-type sequences. Several specific protein binding sites have been identified within the centromeric K-type repeat, consistent with a recently proposed model for centromere/kinetochore function in S. pombe.
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Bodor, Dani L., Luis P. Valente, João F. Mata, Ben E. Black, and Lars E. T. Jansen. "Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomes." Molecular Biology of the Cell 24, no. 7 (April 2013): 923–32. http://dx.doi.org/10.1091/mbc.e13-01-0034.
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Centromeres are the site of kinetochore formation during mitosis. Centromere protein A (CENP-A), the centromere-specific histone H3 variant, is essential for the epigenetic maintenance of centromere position. Previously we showed that newly synthesized CENP-A is targeted to centromeres exclusively during early G1 phase and is subsequently maintained across mitotic divisions. Using SNAP-based fluorescent pulse labeling, we now demonstrate that cell cycle–restricted chromatin assembly at centromeres is unique to CENP-A nucleosomes and does not involve assembly of other H3 variants. Strikingly, stable retention is restricted to the CENP-A/H4 core of the nucleosome, which we find to outlast general chromatin across several cell divisions. We further show that cell cycle timing of CENP-A assembly is independent of centromeric DNA sequences and instead is mediated by the CENP-A targeting domain. Unexpectedly, this domain also induces stable transmission of centromeric nucleosomes, independent of the CENP-A deposition factor HJURP. This demonstrates that intrinsic properties of the CENP-A protein direct its cell cycle–restricted assembly and induces quantitative mitotic transmission of the CENP-A/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position.
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Giunta, Simona, and Hironori Funabiki. "Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T." Proceedings of the National Academy of Sciences 114, no. 8 (February 6, 2017): 1928–33. http://dx.doi.org/10.1073/pnas.1615133114.
Full textAbstract:
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence. To understand the mechanism(s) that maintains centromere integrity, we examined the contribution of the centromere-specific histone variant CENP-A and members of the constitutive centromere-associated network (CCAN), CENP-C, CENP-T, and CENP-W. Depletion of CENP-A and CCAN proteins led to an increase in centromere aberrations, whereas enhancing chromosome missegregation by alternative methods did not, suggesting that CENP-A and CCAN proteins help maintain centromere integrity independently of their role in chromosome segregation. Furthermore, superresolution imaging of centromeric CO-FISH using structured illumination microscopy implied that CENP-A protects α-satellite repeats from extensive rearrangements. Our study points toward the presence of a centromere-specific mechanism that actively maintains α-satellite repeat integrity during human cell proliferation.
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Jin, Q. W., J. Fuchs, and J. Loidl. "Centromere clustering is a major determinant of yeast interphase nuclear organization." Journal of Cell Science 113, no. 11 (June 1, 2000): 1903–12. http://dx.doi.org/10.1242/jcs.113.11.1903.
Full textAbstract:
During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub. Opposite to the centromeric pole is the nucleolus. Chromosome arms extend outwards from the centromeric pole and are preferentially directed towards the opposite pole. Centromere clustering is reduced by the ndc10 mutation, which affects a kinetochore protein, and by the microtubule poison nocodazole. This suggests that clustering is actively maintained or enforced by the association of centromeres with microtubules throughout interphase. Unlike the Rabl-orientation known from many higher eukaryotes, centromere clustering in yeast is not only a relic of anaphase chromosome polarization, because it can be reconstituted without the passage of cells through anaphase. Within the rosette, homologous centromeres are not arranged in a particular order that would suggest somatic pairing or genome separation.
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Rošić, Silvana, Florian Köhler, and Sylvia Erhardt. "Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division." Journal of Cell Biology 207, no. 3 (November 3, 2014): 335–49. http://dx.doi.org/10.1083/jcb.201404097.
Full textAbstract:
Chromosome segregation requires centromeres on every sister chromatid to correctly form and attach the microtubule spindle during cell division. Even though centromeres are essential for genome stability, the underlying centromeric DNA is highly variable in sequence and evolves quickly. Epigenetic mechanisms are therefore thought to regulate centromeres. Here, we show that the 359-bp repeat satellite III (SAT III), which spans megabases on the X chromosome of Drosophila melanogaster, produces a long noncoding RNA that localizes to centromeric regions of all major chromosomes. Depletion of SAT III RNA causes mitotic defects, not only of the sex chromosome but also in trans of all autosomes. We furthermore find that SAT III RNA binds to the kinetochore component CENP-C, and is required for correct localization of the centromere-defining proteins CENP-A and CENP-C, as well as outer kinetochore proteins. In conclusion, our data reveal that SAT III RNA is an integral part of centromere identity, adding RNA to the complex epigenetic mark at centromeres in flies.
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Roy, Babhrubahan, and Kaustuv Sanyal. "Diversity in Requirement of Genetic and Epigenetic Factors for Centromere Function in Fungi." Eukaryotic Cell 10, no. 11 (September 9, 2011): 1384–95. http://dx.doi.org/10.1128/ec.05165-11.
Full textAbstract:
ABSTRACT A centromere is a chromosomal region on which several proteins assemble to form the kinetochore. The centromere-kinetochore complex helps in the attachment of chromosomes to spindle microtubules to mediate segregation of chromosomes to daughter cells during mitosis and meiosis. In several budding yeast species, the centromere forms in a DNA sequence-dependent manner, whereas in most other fungi, factors other than the DNA sequence also determine the centromere location, as centromeres were able to form on nonnative sequences (neocentromeres) when native centromeres were deleted in engineered strains. Thus, in the absence of a common DNA sequence, the cues that have facilitated centromere formation on a specific DNA sequence for millions of years remain a mystery. Kinetochore formation is facilitated by binding of a centromere-specific histone protein member of the centromeric protein A (CENP-A) family that replaces a canonical histone H3 to form a specialized centromeric chromatin structure. However, the process of kinetochore formation on the rapidly evolving and seemingly diverse centromere DNAs in different fungal species is largely unknown. More interestingly, studies in various yeasts suggest that the factors required for de novo centromere formation (establishment) may be different from those required for maintenance (propagation) of an already established centromere. Apart from the DNA sequence and CENP-A, many other factors, such as posttranslational modification (PTM) of histones at centric and pericentric chromatin, RNA interference, and DNA methylation, are also involved in centromere formation, albeit in a species-specific manner. In this review, we discuss how several genetic and epigenetic factors influence the evolution of structure and function of centromeres in fungal species.
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Dong, Qianhua, Jinpu Yang, Jinxin Gao, and Fei Li. "Recent insights into mechanisms preventing ectopic centromere formation." Open Biology 11, no. 9 (September 2021): 210189. http://dx.doi.org/10.1098/rsob.210189.
Full textAbstract:
The centromere is a specialized chromosomal structure essential for chromosome segregation. Centromere dysfunction leads to chromosome segregation errors and genome instability. In most eukaryotes, centromere identity is specified epigenetically by CENP-A, a centromere-specific histone H3 variant. CENP-A replaces histone H3 in centromeres, and nucleates the assembly of the kinetochore complex. Mislocalization of CENP-A to non-centromeric regions causes ectopic assembly of CENP-A chromatin, which has a devastating impact on chromosome segregation and has been linked to a variety of human cancers. How non-centromeric regions are protected from CENP-A misincorporation in normal cells is largely unexplored. Here, we review the most recent advances on the mechanisms underlying the prevention of ectopic centromere formation, and discuss the implications in human disease.
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Van Hooser, Aaron A., Ilia I. Ouspenski, Heather C. Gregson, Daniel A. Starr, Tim J. Yen, Michael L. Goldberg, Kyoko Yokomori, William C. Earnshaw, Kevin F. Sullivan, and B. R. Brinkley. "Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A." Journal of Cell Science 114, no. 19 (October 1, 2001): 3529–42. http://dx.doi.org/10.1242/jcs.114.19.3529.
Full textAbstract:
The mechanisms that specify precisely where mammalian kinetochores form within arrays of centromeric heterochromatin remain largely unknown. Localization of CENP-A exclusively beneath kinetochore plates suggests that this distinctive histone might direct kinetochore formation by altering the structure of heterochromatin within a sub-region of the centromere. To test this hypothesis, we experimentally mistargeted CENP-A to non-centromeric regions of chromatin and determined whether other centromere-kinetochore components were recruited. CENP-A-containing non-centromeric chromatin assembles a subset of centromere-kinetochore components, including CENP-C, hSMC1, and HZwint-1 by a mechanism that requires the unique CENP-A N-terminal tail. The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected. Experimental mistargeting of CENP-A to inactive centromeres or to acentric double-minute chromosomes was also not sufficient to assemble complete kinetochore activity. The recruitment of centromere-kinetochore proteins to chromatin appears to be a unique function of CENP-A, as the mistargeting of other components was not sufficient for assembly of the same complex. Our results indicate at least two distinct steps in kinetochore assembly: (1) precise targeting of CENP-A, which is sufficient to assemble components of a centromere-prekinetochore scaffold; and (2) targeting of kinetochore microtubule-associated proteins by an additional mechanism present only at active centromeres.
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Guin, Krishnendu, Lakshmi Sreekumar, and Kaustuv Sanyal. "Implications of the Evolutionary Trajectory of Centromeres in the Fungal Kingdom." Annual Review of Microbiology 74, no. 1 (September 8, 2020): 835–53. http://dx.doi.org/10.1146/annurev-micro-011720-122512.
Full textAbstract:
Chromosome segregation during the cell cycle is an evolutionarily conserved, fundamental biological process. Dynamic interaction between spindle microtubules and the kinetochore complex that assembles on centromere DNA is required for faithful chromosome segregation. The first artificial minichromosome was constructed by cloning the centromere DNA of the budding yeast Saccharomyces cerevisiae. Since then, centromeres have been identified in >60 fungal species. The DNA sequence and organization of the sequence elements are highly diverse across these fungal centromeres. In this article, we provide a comprehensive view of the evolution of fungal centromeres. Studies of this process facilitated the identification of factors influencing centromere specification, maintenance, and propagation through many generations. Additionally, we discuss the unique features and plasticity of centromeric chromatin and the involvement of centromeres in karyotype evolution. Finally, we discuss the implications of recurrent loss of RNA interference (RNAi) and/or heterochromatin components on the trajectory of the evolution of fungal centromeres and propose the centromere structure of the last common ancestor of three major fungal phyla—Ascomycota, Basidiomycota, and Mucoromycota.
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Henikoff, Jorja G., Jitendra Thakur, Sivakanthan Kasinathan, and Steven Henikoff. "A unique chromatin complex occupies young α-satellite arrays of human centromeres." Science Advances 1, no. 1 (February 2015): e1400234. http://dx.doi.org/10.1126/sciadv.1400234.
Full textAbstract:
The intractability of homogeneous α-satellite arrays has impeded understanding of human centromeres. Artificial centromeres are produced from higher-order repeats (HORs) present at centromere edges, although the exact sequences and chromatin conformations of centromere cores remain unknown. We use high-resolution chromatin immunoprecipitation (ChIP) of centromere components followed by clustering of sequence data as an unbiased approach to identify functional centromere sequences. We find that specific dimeric α-satellite units shared by multiple individuals dominate functional human centromeres. We identify two recently homogenized α-satellite dimers that are occupied by precisely positioned CENP-A (cenH3) nucleosomes with two ~100–base pair (bp) DNA wraps in tandem separated by a CENP-B/CENP-C–containing linker, whereas pericentromeric HORs show diffuse positioning. Precise positioning is largely maintained, whereas abundance decreases exponentially with divergence, which suggests that young α-satellite dimers with paired ~100-bp particles mediate evolution of functional human centromeres. Our unbiased strategy for identifying functional centromeric sequences should be generally applicable to tandem repeat arrays that dominate the centromeres of most eukaryotes.
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Niikura,, Yohei, Risa Kitagawa, and Katsumi Kitagawa. "CENP-A Ubiquitylation Contributes to Maintaining the Chromosomal Location of the Centromere." Molecules 24, no. 3 (January 22, 2019): 402. http://dx.doi.org/10.3390/molecules24030402.
Full textAbstract:
The centromere plays an essential role in accurate chromosome segregation, and the chromosomal location of the centromere is determined by the presence of a histone H3 variant, centromere protein A (CENP-A), in centromeric nucleosomes. However, the precise mechanisms of deposition, maintenance, and inheritance of CENP-A at centromeres are unclear. We have reported that CENP-A deposition requires ubiquitylation of CENP-A lysine 124 mediated by the E3 ligase activity of Cullin 4A (CUL4A)—RING-box protein 1 (RBX1)—COP9 signalsome complex subunit 8 (COPS8). We have proposed a model of inheritance for CENP-A ubiquitylation, through dimerization between rounds of cell divisions, that maintains the position of centromeres.
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Pluta, A. F., N. Saitoh, I. Goldberg, and W. C. Earnshaw. "Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere." Journal of Cell Biology 116, no. 5 (March 1, 1992): 1081–93. http://dx.doi.org/10.1083/jcb.116.5.1081.
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We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha-satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres.
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He, D., and B. R. Brinkley. "Structure and dynamic organization of centromeres/prekinetochores in the nucleus of mammalian cells." Journal of Cell Science 109, no. 11 (November 1, 1996): 2693–704. http://dx.doi.org/10.1242/jcs.109.11.2693.
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Although considerable research has been focused on understanding the structure and molecular organization of the centromere-kinetochore complex of mitotic chromosomes, few reports have dealt with the centromere (prekinetochore) in the interphase nucleus. In the present study, we utilized anti-centromere antibodies from the serum of patients with the autoimmune disease, scleroderma CREST (calcinosis, Raynaud's phenomenon, esophageal dismotility, sclerodactyly, telangiectasia), as probes to investigate the structure and morphogenesis of the centromere in interphase nuclei of three cell lines using laser scanning confocal microscopy and immunoelectron microscopy. Of particular interest were the chromosomes of the Indian muntjac (2n = 6 in females and 2n = 7 in males), whose large centromeres are thought to have evolved through the tandem fusion of smaller centromeres of a Chinese muntjac-like progenitor species (2n = 46). The various forms and patterns of centromeres observed in the nucleus correlated with stages in the cell cycle as determined by bromodeoxyuridine labeling and apparently represent stages in prereplication, replication and maturation. Immunoelectron microscopic studies using CREST antisera indicated that the high order structure of chromatin associated with each prekinetochore undergoes a regular unfolding-refolding cycle, displaying small bead-like subunits tandemly arranged along a linear thread of centromeric DNA, much like that reported for mitotic chromosomes. Individual centromeres/prekinetochores form a stable association with the 9–13 nm core filaments of the nucleoskeletal network in the nucleus that later become the chromosome scaffold of mitotic chromosomes. Our findings provide morphological support for the hypothesis that the spatial arrangements of individual centromeres within the nucleus may have influenced centromeric translocations and fusions during chromosome evolution. Therefore, the centromere-kinetochore complex, best known for its essential role in partitioning chromosomes in mitosis and meiosis, may also function in chromosome movements and associations in interphase.
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Jansen, Lars E. T., Ben E. Black, Daniel R. Foltz, and Don W. Cleveland. "Propagation of centromeric chromatin requires exit from mitosis." Journal of Cell Biology 176, no. 6 (March 5, 2007): 795–805. http://dx.doi.org/10.1083/jcb.200701066.
Full textAbstract:
Centromeres direct chromosomal inheritance by nucleating assembly of the kinetochore, a large multiprotein complex required for microtubule attachment during mitosis. Centromere identity in humans is epigenetically determined, with no DNA sequence either necessary or sufficient. A prime candidate for the epigenetic mark is assembly into centromeric chromatin of centromere protein A (CENP-A), a histone H3 variant found only at functional centromeres. A new covalent fluorescent pulse-chase labeling approach using SNAP tagging has now been developed and is used to demonstrate that CENP-A bound to a mature centromere is quantitatively and equally partitioned to sister centromeres generated during S phase, thereby remaining stably associated through multiple cell divisions. Loading of nascent CENP-A on the megabase domains of replicated centromere DNA is shown to require passage through mitosis but not microtubule attachment. Very surprisingly, assembly and stabilization of new CENP-A–containing nucleosomes is restricted exclusively to the subsequent G1 phase, demonstrating direct coupling between progression through mitosis and assembly/maturation of the next generation of centromeres.
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Ngan, V. K., and L. Clarke. "The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe." Molecular and Cellular Biology 17, no. 6 (June 1997): 3305–14. http://dx.doi.org/10.1128/mcb.17.6.3305.
Full textAbstract:
The centromere enhancer is a functionally important DNA region within the Schizosaccharomyces pombe centromeric K-type repeat. We have previously shown that addition of the enhancer and cen2 centromeric central core to a circular minichromosome is sufficient to impart appreciable centromere function. A more detailed analysis of the enhancer shows that it is dispensable for centromere function in a cen1-derived minichromosome containing the central core and the remainder of the K-type repeat, indicating that the critical centromeric K-type repeat, like the central core, is characterized by functional redundancy. The centromeric enhancer is required, however, for a central core-carrying minichromosome to exhibit immediate centromere activity when the circular DNA is introduced via transformation into S. pombe. This immediate activation is probably a consequence of a centromere-targeted epigenetic system that governs the chromatin architecture of the region. Moreover, our studies show that two entirely different DNA sequences, consisting of elements derived from two native centromeres, can display centromere function. An S. pombe CENP-B-like protein, Abp1p/Cbp1p, which is required for proper chromosome segregation in vivo, binds in vitro to sites within and adjacent to the modular centromere enhancer, as well as within the centromeric central cores. These results provide direct evidence in fission yeast of a model, similar to one proposed for mammalian systems, whereby no specific sequence is necessary for centromere function but certain classes of sequences are competent to build the appropriate chromatin foundation upon which the centromere/kinetochore can be formed and activated.
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Perpelescu, Marinela, Naohito Nozaki, Chikashi Obuse, Hua Yang, and Kinya Yoda. "Active establishment of centromeric CENP-A chromatin by RSF complex." Journal of Cell Biology 185, no. 3 (April 27, 2009): 397–407. http://dx.doi.org/10.1083/jcb.200903088.
Full textAbstract:
Centromeres are chromosomal structures required for equal DNA segregation to daughter cells, comprising specialized nucleosomes containing centromere protein A (CENP-A) histone, which provide the basis for centromeric chromatin assembly. Discovery of centromere protein components is progressing, but knowledge related to their establishment and maintenance remains limited. Previously, using anti-CENP-A native chromatin immunoprecipitation, we isolated the interphase–centromere complex (ICEN). Among ICEN components, subunits of the remodeling and spacing factor (RSF) complex, Rsf-1 and SNF2h proteins, were found. This paper describes the relationship of the RSF complex to centromere structure and function, demonstrating its requirement for maintenance of CENP-A at the centromeric core chromatin in HeLa cells. The RSF complex interacted with CENP-A chromatin in mid-G1. Rsf-1 depletion induced loss of centromeric CENP-A, and purified RSF complex reconstituted and spaced CENP-A nucleosomes in vitro. From these data, we propose the RSF complex as a new factor actively supporting the assembly of CENP-A chromatin.
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Karalezli, Ilknur, Ayse Gul Zamani, Yunus Emre Goger, Huseyin Osman Yilmaz, and Giray Karalezli. "Evaluation of Centromer H Protein (CENPH) Gene Expression in Prostate Cancers." Selcuk Tip Dergisi 2, no. 37 (June 1, 2021): 151–57. http://dx.doi.org/10.30733/std.2021.01507.
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Scelfo and Fachinetti. "Keeping the Centromere under Control: A Promising Role for DNA Methylation." Cells 8, no. 8 (August 16, 2019): 912. http://dx.doi.org/10.3390/cells8080912.
Full textAbstract:
In order to maintain cell and organism homeostasis, the genetic material has to be faithfully and equally inherited through cell divisions while preserving its integrity. Centromeres play an essential task in this process; they are special sites on chromosomes where kinetochores form on repetitive DNA sequences to enable accurate chromosome segregation. Recent evidence suggests that centromeric DNA sequences, and epigenetic regulation of centromeres, have important roles in centromere physiology. In particular, DNA methylation is abundant at the centromere, and aberrant DNA methylation, observed in certain tumors, has been correlated to aneuploidy and genomic instability. In this review, we evaluate past and current insights on the relationship between centromere function and the DNA methylation pattern of its underlying sequences.
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Giunta, Simona, Solène Hervé, Ryan R. White, Therese Wilhelm, Marie Dumont, Andrea Scelfo, Riccardo Gamba, et al. "CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy." Proceedings of the National Academy of Sciences 118, no. 10 (March 2, 2021): e2015634118. http://dx.doi.org/10.1073/pnas.2015634118.
Full textAbstract:
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats to prevent structural aneuploidy. Rapid removal of CENP-A in S phase, but not other cell-cycle stages, caused accumulation of R loops with increased centromeric transcripts, and interfered with replication fork progression. Replication without CENP-A causes recombination at alpha-satellites in an R loop-dependent manner, unfinished replication, and anaphase bridges. In turn, chromosome breakage and translocations arise specifically at centromeric regions. Our findings provide insights into how specialized centromeric chromatin maintains the integrity of transcribed noncoding repetitive DNA during S phase.
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Marschall, L. G., and L. Clarke. "A novel cis-acting centromeric DNA element affects S. pombe centromeric chromatin structure at a distance." Journal of Cell Biology 128, no. 4 (February 15, 1995): 445–54. http://dx.doi.org/10.1083/jcb.128.4.445.
Full textAbstract:
The chromatin structure of the central core region of Schizosaccharomyces pombe centromeric DNA is unusual. This distinctive chromatin structure is associated only with central core sequences in a functional context and is modulated by a novel cis-acting DNA element (centromere enhancer) within the functionally critical K centromeric repeat, which is found in multiple copies in all three S. pombe centromeres. The centromere enhancer alters central core chromatin structure from a distance and in an orientation-independent manner without altering the nucleosomal packaging of sequences between the enhancer and the central core. These findings suggest a functionally relevant structural interaction between the enhancer and the centromeric central core brought about by DNA looping.
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Prosée, Reinier F., Joanna M. Wenda, Isa Özdemir, Caroline Gabus, Kamila Delaney, Francoise Schwager, Monica Gotta, and Florian A. Steiner. "Transgenerational inheritance of centromere identity requires the CENP-A N-terminal tail in the C. elegans maternal germ line." PLOS Biology 19, no. 7 (July 6, 2021): e3000968. http://dx.doi.org/10.1371/journal.pbio.3000968.
Full textAbstract:
Centromere protein A (CENP-A) is a histone H3 variant that defines centromeric chromatin and is essential for centromere function. In most eukaryotes, CENP-A-containing chromatin is epigenetically maintained, and centromere identity is inherited from one cell cycle to the next. In the germ line of the holocentric nematode Caenorhabditis elegans, this inheritance cycle is disrupted. CENP-A is removed at the mitosis-to-meiosis transition and is reestablished on chromatin during diplotene of meiosis I. Here, we show that the N-terminal tail of CENP-A is required for the de novo establishment of centromeres, but then its presence becomes dispensable for centromere maintenance during development. Worms homozygous for a CENP-A tail deletion maintain functional centromeres during development but give rise to inviable offspring because they fail to reestablish centromeres in the maternal germ line. We identify the N-terminal tail of CENP-A as a critical domain for the interaction with the conserved kinetochore protein KNL-2 and argue that this interaction plays an important role in setting centromere identity in the germ line. We conclude that centromere establishment and maintenance are functionally distinct in C. elegans.
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Carroll, Christopher W., and Aaron F. Straight. "Centromeric chromatin gets loaded." Journal of Cell Biology 176, no. 6 (March 5, 2007): 735–36. http://dx.doi.org/10.1083/jcb.200702020.
Full textAbstract:
Centromeric nucleosomes contain a histone H3 variant called centromere protein A (CENP-A) that is required for kinetochore assembly and chromosome segregation. Two new studies, Jansen et al. (see p. 795 of this issue) and Maddox et al. (see p. 757 of this issue), address when CENP-A is deposited at centromeres during the cell division cycle and identify an evolutionally conserved protein required for CENP-A deposition. Together, these studies advance our understanding of centromeric chromatin assembly and provide a framework for investigating the molecular mechanisms that underlie the centromere-specific loading of CENP-A.
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Ling, Yick Hin, and Karen Wing Yee Yuen. "Point centromere activity requires an optimal level of centromeric noncoding RNA." Proceedings of the National Academy of Sciences 116, no. 13 (March 8, 2019): 6270–79. http://dx.doi.org/10.1073/pnas.1821384116.
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In budding yeast, which possesses simple point centromeres, we discovered that all of its centromeres express long noncoding RNAs (cenRNAs), especially in S phase. Induction of cenRNAs coincides with CENP-ACse4loading time and is dependent on DNA replication. Centromeric transcription is repressed by centromere-binding factor Cbf1 and histone H2A variant H2A.ZHtz1. Deletion ofCBF1andH2A.ZHTZ1results in an up-regulation of cenRNAs; an increased loss of a minichromosome; elevated aneuploidy; a down-regulation of the protein levels of centromeric proteins CENP-ACse4, CENP-A chaperone HJURPScm3, CENP-CMif2, SurvivinBir1, and INCENPSli15; and a reduced chromatin localization of CENP-ACse4, CENP-CMif2, and Aurora BIpl1. When the RNA interference system was introduced to knock down all cenRNAs from the endogenous chromosomes, but not the cenRNA from the circular minichromosome, an increase in minichromosome loss was still observed, suggesting that cenRNA functionsin transto regulate centromere activity. CenRNA knockdown partially alleviates minichromosome loss incbf1Δ,htz1Δ, andcbf1Δ htz1Δin a dose-dependent manner, demonstrating that cenRNA level is tightly regulated to epigenetically control point centromere function.
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Martins, Nuno M. C., Fernanda Cisneros-Soberanis, Elisa Pesenti, Natalia Y. Kochanova, Wei-Hao Shang, Tetsuya Hori, Takahiro Nagase, et al. "H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory." Journal of Cell Science 133, no. 14 (June 23, 2020): jcs242610. http://dx.doi.org/10.1242/jcs.242610.
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ABSTRACTMost eukaryotic centromeres are located within heterochromatic regions. Paradoxically, heterochromatin can also antagonize de novo centromere formation, and some centromeres lack it altogether. In order to investigate the importance of heterochromatin at centromeres, we used epigenetic engineering of a synthetic alphoidtetO human artificial chromosome (HAC), to which chimeric proteins can be targeted. By tethering the JMJD2D demethylase (also known as KDM4D), we removed heterochromatin mark H3K9me3 (histone 3 lysine 9 trimethylation) specifically from the HAC centromere. This caused no short-term defects, but long-term tethering reduced HAC centromere protein levels and triggered HAC mis-segregation. However, centromeric CENP-A was maintained at a reduced level. Furthermore, HAC centromere function was compatible with an alternative low-H3K9me3, high-H3K27me3 chromatin signature, as long as residual levels of H3K9me3 remained. When JMJD2D was released from the HAC, H3K9me3 levels recovered over several days back to initial levels along with CENP-A and CENP-C centromere levels, and mitotic segregation fidelity. Our results suggest that a minimal level of heterochromatin is required to stabilize mitotic centromere function but not for maintaining centromere epigenetic memory, and that a homeostatic pathway maintains heterochromatin at centromeres.This article has an associated First Person interview with the first authors of the paper.
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Maggert, Keith A., and Gary H. Karpen. "The Activation of a Neocentromere in Drosophila Requires Proximity to an Endogenous Centromere." Genetics 158, no. 4 (August 1, 2001): 1615–28. http://dx.doi.org/10.1093/genetics/158.4.1615.
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AbstractThe centromere is essential for proper segregation and inheritance of genetic information. Centromeres are generally regulated to occur exactly once per chromosome; failure to do so leads to chromosome loss or damage and loss of linked genetic material. The mechanism for faithful regulation of centromere activity and number is unknown. The presence of ectopic centromeres (neocentromeres) has allowed us to probe the requirements and characteristics of centromere activation, maintenance, and structure. We utilized chromosome derivatives that placed a 290-kilobase “test segment” in three different contexts within the Drosophila melanogaster genome—immediately adjacent to (1) centromeric chromatin, (2) centric heterochromatin, or (3) euchromatin. Using irradiation mutagenesis, we freed this test segment from the source chromosome and genetically assayed whether the liberated “test fragment” exhibited centromere activity. We observed that this test fragment behaved differently with respect to centromere activity when liberated from different chromosomal contexts, despite an apparent sequence identity. Test segments juxtaposed to an active centromere produced fragments with neocentromere activity, whereas test segments far from centromeres did not. Once established, neocentromere activity was stable. The imposition of neocentromere activity on juxtaposed DNA supports the hypothesis that centromere activity and identity is capable of spreading and is regulated epigenetically.
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Hasanova, Aytakin. "CHARACTERIZATION OF HUMAN CHROMOSOMAL CONSTITUTIVE HETEROCHROMATIN." Gulustan-Black Sea Scientific Journal of Academic Research 53, no. 02 (April 15, 2020): 08–11. http://dx.doi.org/10.36962/gbssjar5302202008.
Full textAbstract:
Heterochromatin of centromeric chromosome regions contains late replicating, largely repetitive DNA. It is suggested that heterochromatin participates in chromosome pairing, crossing-over and in chromosome disjunction control (1,3). Centromeric heterochromatin, a variety of heterochromatin, is a tightly packed form of DNA.Centromeric heterochromatin is a constituent in the formation ofactive centromeres in most higher-order organisms; the domain exists on both mitotic and interphase chromosomes. (4,5,6,8) Centromeric heterochromatin is usually formed on alpha satellite DNA in humans; however, there have been cases where centric heterochromatin and centromeres have formed on originally euchromatin domains lacking alpha satellite DNA; this usually happens as a result of a chromosome breakage event and the formed centromere is called a neocentromere.
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Bobkov, Georg O. M., Nick Gilbert, and Patrick Heun. "Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation." Journal of Cell Biology 217, no. 6 (April 6, 2018): 1957–72. http://dx.doi.org/10.1083/jcb.201611087.
Full textAbstract:
Centromeres are essential for chromosome segregation and are specified epigenetically by the presence of the histone H3 variant CENP-A. In flies and humans, replenishment of the centromeric mark is uncoupled from DNA replication and requires the removal of H3 “placeholder” nucleosomes. Although transcription at centromeres has been previously linked to the loading of new CENP-A, the underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells to show that centromeric presence of actively transcribing RNA polymerase II temporally coincides with de novo deposition of dCENP-A. Using a newly developed dCENP-A loading system that is independent of acute transcription, we found that short inhibition of transcription impaired dCENP-A incorporation into chromatin. Interestingly, initial targeting of dCENP-A to centromeres was unaffected, revealing two stability states of newly loaded dCENP-A: a salt-sensitive association with the centromere and a salt-resistant chromatin-incorporated form. This suggests that transcription-mediated chromatin remodeling is required for the transition of dCENP-A to fully incorporated nucleosomes at the centromere.
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Hill, Emma, and Ruth Williams. "Super-coil me: Sizing up centromeric nucleosomes." Journal of Cell Biology 186, no. 4 (August 24, 2009): 453–56. http://dx.doi.org/10.1083/jcb.200908012.
Full textAbstract:
Every chromosome needs a centromere for proper segregation during cell division. Centromeric chromatin wraps around histones, providing an anchor for kinetochore proteins and spindle attachment. It is clear why cells need centromeres, but how they form and what they look like is less so. Recent reports extend our understanding of chaperones involved in centromere formation. And other accounts of half-sized, right-handed nucleosomes have created an unexpected twist.
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Perpelescu, Marinela, Tetsuya Hori, Atsushi Toyoda, Sadahiko Misu, Norikazu Monma, Kazuho Ikeo, Chikashi Obuse, Asao Fujiyama, and Tatsuo Fukagawa. "HJURP is involved in the expansion of centromeric chromatin." Molecular Biology of the Cell 26, no. 15 (August 2015): 2742–54. http://dx.doi.org/10.1091/mbc.e15-02-0094.
Full textAbstract:
The CENP-A–specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A–binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure.
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Carvalho, Célia, Henrique M. Pereira, João Ferreira, Cristina Pina, Denise Mendonça, Agostinho C. Rosa, and Maria Carmo-Fonseca. "Chromosomal G-dark Bands Determine the Spatial Organization of Centromeric Heterochromatin in the Nucleus." Molecular Biology of the Cell 12, no. 11 (November 2001): 3563–72. http://dx.doi.org/10.1091/mbc.12.11.3563.
Full textAbstract:
Gene expression can be silenced by proximity to heterochromatin blocks containing centromeric α-satellite DNA. This has been shown experimentally through cis-acting chromosome rearrangements resulting in linear genomic proximity, or throughtrans-acting changes resulting in intranuclear spatial proximity. Although it has long been been established that centromeres are nonrandomly distributed during interphase, little is known of what determines the three-dimensional organization of these silencing domains in the nucleus. Here, we propose a model that predicts the intranuclear positioning of centromeric heterochromatin for each individual chromosome. With the use of fluorescence in situ hybridization and confocal microscopy, we show that the distribution of centromeric α-satellite DNA in human lymphoid cells synchronized at G0/G1is unique for most individual chromosomes. Regression analysis reveals a tight correlation between nuclear distribution of centromeric α-satellite DNA and the presence of G-dark bands in the corresponding chromosome. Centromeres surrounded by G-dark bands are preferentially located at the nuclear periphery, whereas centromeres of chromosomes with a lower content of G-dark bands tend to be localized at the nucleolus. Consistent with the model, a t(11; 14) translocation that removes G-dark bands from chromosome 11 causes a repositioning of the centromere, which becomes less frequently localized at the nuclear periphery and more frequently associated with the nucleolus. The data suggest that “chromosomal environment” plays a key role in the intranuclear organization of centromeric heterochromatin. Our model further predicts that facultative heterochromatinization of distinct genomic regions may contribute to cell-type specific patterns of centromere localization.
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Previato de Almeida, Luciana, Jared M. Evatt, Hoa H. Chuong, Emily L. Kurdzo, Craig A. Eyster, Mara N. Gladstone, Laura Gómez-H, et al. "Shugoshin protects centromere pairing and promotes segregation of nonexchange partner chromosomes in meiosis." Proceedings of the National Academy of Sciences 116, no. 19 (April 24, 2019): 9417–22. http://dx.doi.org/10.1073/pnas.1902526116.
Full textAbstract:
Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.