Log in

Relevant bibliographies by topics / TDPX2 / Journal articles

To see the other types of publications on this topic, follow the link: TDPX2.

Journal articles on the topic 'TDPX2'

Author: Grafiati

Published: 4 June 2025

Last updated: 15 July 2025

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'TDPX2.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Schellenberg, Matthew J., C. Denise Appel, Amanda A. Riccio, et al. "Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2." Nucleic Acids Research 48, no. 11 (2020): 6310–25. http://dx.doi.org/10.1093/nar/gkaa318.

Full text

Abstract:

Abstract Tyrosyl-DNA phosphodiesterase 2 (TDP2) reverses Topoisomerase 2 DNA–protein crosslinks (TOP2-DPCs) in a direct-reversal pathway licensed by ZATTZNF451 SUMO2 E3 ligase and SUMOylation of TOP2. TDP2 also binds ubiquitin (Ub), but how Ub regulates TDP2 functions is unknown. Here, we show that TDP2 co-purifies with K63 and K27 poly-Ubiquitinated cellular proteins independently of, and separately from SUMOylated TOP2 complexes. Poly-ubiquitin chains of ≥ Ub3 stimulate TDP2 catalytic activity in nuclear extracts and enhance TDP2 binding of DNA–protein crosslinks in vitro. X-ray crystal structures and small-angle X-ray scattering analysis of TDP2-Ub complexes reveal that the TDP2 UBA domain binds K63-Ub3 in a 1:1 stoichiometric complex that relieves a UBA-regulated autoinhibitory state of TDP2. Our data indicates that that poly-Ub regulates TDP2-catalyzed TOP2-DPC removal, and TDP2 single nucleotide polymorphisms can disrupt the TDP2-Ubiquitin interface.

APA, Harvard, Vancouver, ISO, and other styles

2

Hornyak, Peter, Trevor Askwith, Sarah Walker, et al. "Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2." Biochemical Journal 473, no. 13 (2016): 1869–79. http://dx.doi.org/10.1042/bcj20160180.

Full text

Abstract:

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a 5′-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II (TOP2). TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for high-throughput screen (HTS)-screening. We have gone on to determine crystal structures of these compounds bound to a ‘humanized’ form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2.

APA, Harvard, Vancouver, ISO, and other styles

3

Lee, Ka, Rebecca Swan, Zbyslaw Sondka, Kay Padget, Ian Cowell, and Caroline Austin. "Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes." International Journal of Molecular Sciences 19, no. 7 (2018): 2056. http://dx.doi.org/10.3390/ijms19072056.

Full text

Abstract:

DNA topoisomerase II (TOP2) activity involves a normally transient double-strand break intermediate in which the enzyme is coupled to DNA via a 5′-phosphotyrosyl bond. However, etoposide and other topoisomerase drugs poison the enzyme by stabilising this enzyme-bridged break, resulting in the accumulation of TOP2-DNA covalent complexes with cytotoxic consequences. The phosphotyrosyl diesterase TDP2 appears to be required for efficient repair of this unusual type of DNA damage and can remove 5′-tyrosine adducts from a double-stranded oligonucleotide substrate. Here, we adapt the trapped in agarose DNA immunostaining (TARDIS) assay to investigate the role of TDP2 in the removal of TOP2-DNA complexes in vitro and in cells. We report that TDP2 alone does not remove TOP2-DNA complexes from genomic DNA in vitro and that depletion of TDP2 in cells does not slow the removal of TOP2-DNA complexes. Thus, if TDP2 is involved in repairing TOP2 adducts, there must be one or more prior steps in which the protein-DNA complex is processed before TDP2 removes the remaining 5′ tyrosine DNA adducts. While this is partly achieved through the degradation of TOP2 adducts by the proteasome, a proteasome-independent mechanism has also been described involving the SUMOylation of TOP2 by the ZATT E3 SUMO ligase. The TARDIS assay was also adapted to measure the effect of TDP2 knockdown on levels of SUMOylated TOP2-DNA complexes, which together with levels of double strand breaks were unaffected in K562 cells following etoposide exposure and proteasomal inhibition.

APA, Harvard, Vancouver, ISO, and other styles

4

Schellenberg, Matthew J., Jenna Ariel Lieberman, Andrés Herrero-Ruiz, et al. "ZATT (ZNF451)–mediated resolution of topoisomerase 2 DNA-protein cross-links." Science 357, no. 6358 (2017): 1412–16. http://dx.doi.org/10.1126/science.aam6468.

Full text

Abstract:

Topoisomerase 2 (TOP2) DNA transactions proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO (small ubiquitin-related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc. The ZATT SUMO ligase activity further promotes TDP2 interactions with SUMOylated TOP2, regulating efficient TDP2 recruitment through a “split-SIM” SUMO2 engagement platform. These findings uncover a ZATT-TDP2–catalyzed and SUMO2-modulated pathway for direct resolution of TOP2cc.

APA, Harvard, Vancouver, ISO, and other styles

5

Huang, Shar-yin Naomi, and Yves Pommier. "Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair." International Journal of Molecular Sciences 20, no. 12 (2019): 3015. http://dx.doi.org/10.3390/ijms20123015.

Full text

Abstract:

Mammalian mitochondria contain four topoisomerases encoded in the nuclear genome: TOP1MT, TOP2α, TOP2β, and TOP3α. They also contain the two known tyrosyl-DNA phosphodiesterases (TDPs): TDP1 and TDP2, including a specific TDP2S isoform. Both TDP1 and TDP2 excise abortive topoisomerase cleavage complexes (TOPccs), yet their molecular structures and mechanisms are different. TDP1 is present across eukaryotes, from yeasts to humans and belongs to the phospholipase D family. It functions without a metal cofactor and has a broad activity range, as it also serves to cleanse blocking 3′-DNA ends bearing phosphoglycolate, deoxyribose phosphate, nucleoside, nucleoside analogs (zidovudine), abasic moieties, and with a lower efficiency, TOP2ccs. Found in higher vertebrates, TDP2 is absent in yeast where TDP1 appears to perform its functions. TDP2 belongs to the exonuclease/endonuclease/phosphodiesterase family and requires magnesium as a cofactor to excise TOP2ccs, and it also excises TOP1ccs, albeit with a lower efficiency. Here, we review TDP1 and TDP2 in the context of mitochondrial DNA repair and discuss potential new research areas centered on the mitochondrial TDPs.

APA, Harvard, Vancouver, ISO, and other styles

6

Zakharenko, Alexandra L., Nadezhda S. Dyrkheeva, Olga A. Luzina, et al. "Usnic Acid Derivatives Inhibit DNA Repair Enzymes Tyrosyl-DNA Phosphodiesterases 1 and 2 and Act as Potential Anticancer Agents." Genes 14, no. 10 (2023): 1931. http://dx.doi.org/10.3390/genes14101931.

Full text

Abstract:

Tyrosyl-DNA phosphodiesterase 1 and 2 (Tdp1 and Tdp2) are DNA repair enzymes that repair DNA damage caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reason for resistance to such widely used drugs such as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (−)-usnic acid. Both (+)- and (−)-enantiomers of compounds act equally effectively against Tdp1 with IC50 values in the range of 0.02–0.2 μM; only (−)-enantiomers inhibited Tdp2 with IC50 values in the range of 6–9 μM. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide (CC50 3.0–3.9 μM in the presence of compounds and 2.4 μM the presence of DMSO) but potentiate it against Tdp2 knockout cells (CC50 1.2–1.6 μM in the presence of compounds against 2.3 μM in the presence of DMSO). We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with the effective inhibition of Tdp1, which could take over the functions of Tdp2.

APA, Harvard, Vancouver, ISO, and other styles

7

Park, Jeong-Min, Huimin Zhang, Litong Nie, et al. "Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway." International Journal of Molecular Sciences 24, no. 7 (2023): 6545. http://dx.doi.org/10.3390/ijms24076545.

Full text

Abstract:

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2–DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5′-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1–168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy.

APA, Harvard, Vancouver, ISO, and other styles

8

Holmes, Autumn C., Guido Zagnoli-Vieira, Keith W. Caldecott, and Bert L. Semler. "Effects of TDP2/VPg Unlinkase Activity on Picornavirus Infections Downstream of Virus Translation." Viruses 12, no. 2 (2020): 166. http://dx.doi.org/10.3390/v12020166.

Full text

Abstract:

In this study, we characterized the role of host cell protein tyrosyl-DNA phosphodiesterase 2 (TDP2) activity, also known as VPg unlinkase, in picornavirus infections in a human cell model of infection. TDP2/VPg unlinkase is used by picornaviruses to remove the small polypeptide, VPg (Virus Protein genome-linked, the primer for viral RNA synthesis), from virus genomic RNA. We utilized a CRISPR/Cas-9-generated TDP2 knock out (KO) human retinal pigment epithelial-1 (hRPE-1) cell line, in addition to the wild type (WT) counterpart for our studies. We determined that in the absence of TDP2, virus growth kinetics for two enteroviruses (poliovirus and coxsackievirus B3) were delayed by about 2 h. Virus titers were reduced by ~2 log10 units for poliovirus and 0.5 log10 units for coxsackievirus at 4 hours post-infection (hpi), and by ~1 log10 unit at 6 hpi for poliovirus. However, virus titers were nearly indistinguishable from those of control cells by the end of the infectious cycle. We determined that this was not the result of an alternative source of VPg unlinkase activity being activated in the absence of TPD2 at late times of infection. Viral protein production in TDP2 KO cells was also substantially reduced at 4 hpi for poliovirus infection, consistent with the observed growth kinetics delay, but reached normal levels by 6 hpi. Interestingly, this result differs somewhat from what has been reported previously for the TDP2 KO mouse cell model, suggesting that either cell type or species-specific differences might be playing a role in the observed phenotype. We also determined that catalytically inactive TDP2 does not rescue the growth defect, confirming that TDP2 5′ phosphodiesterase activity is required for efficient virus replication. Importantly, we show for the first time that polysomes can assemble efficiently on VPg-linked RNA after the initial round of translation in a cell culture model, but both positive and negative strand RNA production is impaired in the absence of TDP2 at mid-times of infection, indicating that the presence of VPg on the viral RNA affects a step in the replication cycle downstream of translation (e.g., RNA synthesis). In agreement with this conclusion, we found that double-stranded RNA production (a marker of viral RNA synthesis) is delayed in TDP2 KO RPE-1 cells. Moreover, we show that premature encapsidation of nascent, VPg-linked RNA is not responsible for the observed virus growth defect. Our studies provide the first lines of evidence to suggest that either negative- or positive-strand RNA synthesis (or both) is a likely candidate for the step that requires the removal of VPg from the RNA for an enterovirus infection to proceed efficiently.

APA, Harvard, Vancouver, ISO, and other styles

9

Kan, Chau Ming, Xiao Meng Pei, Simon Siu Man Ng, et al. "Validation of Prognostic Circulating Cell-Free RNA Biomarkers HPGD, PACS1, and TDP2 in Colorectal Cancer Through TaqMan qPCR and Correlation Analysis." Current Issues in Molecular Biology 47, no. 7 (2025): 508. https://doi.org/10.3390/cimb47070508.

Full text

Abstract:

Circulating cell-free RNAs (cfRNAs) have emerged as promising non-invasive biomarkers for colorectal cancer (CRC), offering insights into the disease’s prognosis. This study investigates the prognostic significance of the specific cfRNA biomarkers HPGD, PACS1, and TDP2 by employing the Taqman quantitative PCR (qPCR) to evaluate their expression levels in a cohort of 52 CRC patients. The methodology involved a robust statistical analysis to assess correlations between cfRNA levels and clinical parameters, including survival rates and recurrence incidences. Findings revealed a significant upregulation in the expression of HPGD and PACS1, while TDP2 displayed varying results, indicating a complex role in disease dynamics. Notably, lower expression levels of HPGD were associated with reduced survival, suggesting its potential as a negative prognostic indicator. Conversely, TDP2 levels correlated strongly with increased risks of recurrence, highlighting its clinical relevance in monitoring disease progression. Overall, this study elucidates the intricate interplay between these cfRNAs in the CRC prognosis. The results advocate for further exploratory studies to validate PACS1’s potential as a prognostic marker and reinforce the clinical significance of HPGD and TDP2 in the context of CRC management, positioning them as vital elements in the landscape of molecular oncology.

APA, Harvard, Vancouver, ISO, and other styles

10

Filimonov, Aleksandr S., Marina A. Mikhailova, Nadezhda S. Dyrkheeva, et al. "Sulfide, Sulfoxide, and Sulfone Derivatives of Usnic Acid as Inhibitors of Human TDP1 and TDP2 Enzymes." Chemistry 6, no. 6 (2024): 1658–79. https://doi.org/10.3390/chemistry6060101.

Full text

Abstract:

Tyrosyl-DNA phosphodiesterases 1 and 2 (TDP1 and TDP2) are important DNA repair enzymes that remove various adducts from the 3′- and 5′-ends of DNA, respectively. The suppression of the activity of these enzymes is considered as a promising adjuvant therapy for oncological diseases in combination with topoisomerase inhibitors. The simultaneous inhibition of TDP1 and TDP2 may result in greater antitumor effects, as these enzymes can mimic each other’s functions. We have previously shown that usnic acid-based sulfides can act as dual inhibitors, with TDP1 activity in the low micromolar range and their TDP2 at 1 mM. The oxidation of their sulfide moieties to sulfoxides led to an order of magnitude decrease in their cytotoxicity potential, while their TDP1 and TDP2 activity was preserved. In this work, we synthesized new series of usnic acid-based sulfides and their oxidized analogues, i.e., sulfoxides and sulfones, to systematically study these irregularities. The new compounds inhibit TDP1 with IC50 values (the concentration of inhibitor required to reduce enzyme activity by half) in the 0.33–25 μM range. Most sulfides and some sulfoxides and sulfones inhibit TDP2 with an IC50 = 138−421 μM. In addition, the most active compounds synergized (×4) with topotecan on the HeLa cell line as well as causing dose-dependent DNA damage, as confirmed by Comet assay. Sulfides with the 6-methylbenzoimidazol-2-yl substituent (8f, IC50 = 0.33/138 μM, TDP1/2) and sulfones containing a pyridine-2-yl fragment (12k, IC50 = 2/228 μM, TDP1/2) are the most potent derivatives and, therefore, are promising for further development.

APA, Harvard, Vancouver, ISO, and other styles

11

Salomatina, Oksana V., Nadezhda S. Dyrkheeva, Irina I. Popadyuk, et al. "New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2." Molecules 27, no. 1 (2021): 72. http://dx.doi.org/10.3390/molecules27010072.

Full text

Abstract:

A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration. Tryptamide 5 and para-bromoanilide 8 derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to molecular modeling, ligand 5 is anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π–π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. It can therefore be concluded that these derivatives contribute to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons.

APA, Harvard, Vancouver, ISO, and other styles

12

Salomatina, Oksana V., Tatyana E. Kornienko, Alexandra L. Zakharenko, et al. "New Dual Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 and 2 Based on Deoxycholic Acid: Design, Synthesis, Cytotoxicity, and Molecular Modeling." Molecules 29, no. 3 (2024): 581. http://dx.doi.org/10.3390/molecules29030581.

Full text

Abstract:

Deoxycholic acid derivatives containing various heterocyclic functional groups at C-3 on the steroid scaffold were designed and synthesized as promising dual tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) inhibitors, which are potential targets to potentiate topoisomerase poison antitumor therapy. The methyl esters of DCA derivatives with benzothiazole or benzimidazole moieties at C-3 demonstrated promising inhibitory activity in vitro against TDP1 with IC50 values in the submicromolar range. Furthermore, methyl esters 4d–e, as well as their acid counterparts 3d–e, inhibited the phosphodiesterase activity of both TDP1 and TDP2. The combinations of compounds 3d–e and 4d–e with low-toxic concentrations of antitumor drugs topotecan and etoposide showed significantly greater cytotoxicity than the compounds alone. The docking of the derivatives into the binding sites of TDP1 and TDP2 predicted plausible binding modes of the DCA derivatives.

APA, Harvard, Vancouver, ISO, and other styles

13

Takeishi, Ayuna, Hiroyuki Kogashi, Mizuki Odagiri, et al. "Tyrosyl-DNA phosphodiesterases are involved in mutagenic events at a ribonucleotide embedded into DNA in human cells." PLOS ONE 15, no. 12 (2020): e0244790. http://dx.doi.org/10.1371/journal.pone.0244790.

Full text

Abstract:

Ribonucleoside triphosphates are often incorporated into genomic DNA during DNA replication. The accumulation of unrepaired ribonucleotides is associated with genomic instability, which is mediated by DNA topoisomerase 1 (Top1) processing of embedded ribonucleotides. The cleavage initiated by Top1 at the site of a ribonucleotide leads to the formation of a Top1-DNA cleavage complex (Top1cc), occasionally resulting in a DNA double-strand break (DSB). In humans, tyrosyl-DNA phosphodiesterases (TDPs) are essential repair enzymes that resolve the trapped Top1cc followed by downstream repair factors. However, there is limited cellular evidence of the involvement of TDPs in the processing of incorporated ribonucleotides in mammals. We assessed the role of TDPs in mutagenesis induced by a single ribonucleotide embedded into DNA. A supF shuttle vector site-specifically containing a single riboguanosine (rG) was introduced into the human lymphoblastoid TK6 cell line and its TDP1-, TDP2-, and TDP1/TDP2-deficient derivatives. TDP1 and TDP2 insufficiency remarkably decreased the mutant frequency caused by an embedded rG. The ratio of large deletion mutations induced by rG was also substantially lower in TDP1/TDP2-deficient cells than wild-type cells. Furthermore, the disruption of TDPs reduced the length of rG-mediated large deletion mutations. The recovery ratio of the propagated plasmid was also increased in TDP1/TDP2-deficient cells after the transfection of the shuttle vector containing rG. The results suggest that TDPs-mediated ribonucleotide processing cascade leads to unfavorable consequences, whereas in the absence of these repair factors, a more error-free processing pathway might function to suppress the ribonucleotide-induced mutagenesis. Furthermore, base substitution mutations at sites outside the position of rG were detected in the supF gene via a TDPs-independent mechanism. Overall, we provide new insights into the mechanism of mutagenesis induced by an embedded ribonucleotide in mammalian cells, which may lead to the fatal phenotype in the ribonucleotide excision repair deficiency.

APA, Harvard, Vancouver, ISO, and other styles

14

А.С., ФИЛИМОНОВ, ЧЕПАНОВА А.А., МИХАЙЛОВА М.А. та ін. "СИНТЕЗ НОВЫХ ПРОИЗВОДНЫХ УСНИНОВОЙ КИСЛОТЫ И ИЗУЧЕНИЕ ИХ ИНГИБИРУЮЩЕЙ АКТИВНОСТИ В ОТНОШЕНИИ ТИРОЗИЛ-ДНК-ФОСФОДИЭСТЕРАЗ 1 И 2". Химия в интересах устойчивого развития 31, № 6 (2023): 718–27. http://dx.doi.org/10.15372/khur2023519.

Full text

Abstract:

Тирозил-ДНК-фосфодиэстеразы 1 и 2 (Tdp1 и Tdp2) - ферменты репарации ДНК, которые рассматриваются как потенциальные мишени для вспомогательной противоопухолевой терапии в комбинации с ингибиторами топоизомераз. Наиболее эффективные ингибиторы Tdp1 были обнаружены среди производных вторичного метаболита лишайников усниновой кислоты, сенсибилизирующее действие которых в сочетании с ингибитором топоизомеразы 1 топотеканом подтверждено в экспериментах на культурах клеток и на животных моделях. Описаны новые производные усниновой кислоты, синтезированные на основе ранее полученных ингибиторов Tdp1 путем введения аннелированного с кольцом С дибензофуранового остова пиразольного цикла, что позволяет снизить собственную токсичность получаемых соединений. Найдены новые дуальные ингибиторы Tdp1 и Tdp2 в микромолярном диапазоне концентраций. Tyrosyl-DNA phosphodiesterases 1 and 2 (Tdp1 and Tdp2) are DNA repair enzymes that are considered as potential targets for antitumour supporting therapy in combination with topoisomerase inhibitors. The most effective Tdp1 inhibitors were found among the derivatives of the lichen secondary metabolite usnic acid. The sensitising effect of these compounds in combination with the topoisomerase 1 inhibitor topotecan was confirmed in cell culture experiments and animal models. In the present work, we describe new derivatives of usnic acid synthesized on the basis of previously obtained Tdp1 inhibitors by introducing the pyrazole cycle annelated with the C ring in dibenzofuran backbone, which makes it possible to reduce the intrinsic toxicity of the obtained compounds. New dual Tdp1 and Tdp2 inhibitors in the micromolar range of concentrations are found.

APA, Harvard, Vancouver, ISO, and other styles

15

McKinnon, Peter J. "TDP2 keeps the brain healthy." Nature Genetics 46, no. 5 (2014): 419–21. http://dx.doi.org/10.1038/ng.2967.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Zagnoli-Vieira, Guido, Francesco Bruni, Kyle Thompson, et al. "Confirming TDP2 mutation in spinocerebellar ataxia autosomal recessive 23 (SCAR23)." Neurology Genetics 4, no. 4 (2018): e262. http://dx.doi.org/10.1212/nxg.0000000000000262.

Full text

Abstract:

ObjectiveTo address the relationship between mutations in the DNA strand break repair protein tyrosyl DNA phosphodiesterase 2 (TDP2) and spinocerebellar ataxia autosomal recessive 23 (SCAR23) and to characterize the cellular phenotype of primary fibroblasts from this disease.MethodsWe have used exome sequencing, Sanger sequencing, gene editing and cell biology, biochemistry, and subcellular mitochondrial analyses for this study.ResultsWe have identified a patient in the United States with SCAR23 harboring the same homozygous TDP2 mutation as previously reported in 3 Irish siblings (c.425+1G>A). The current and Irish patients share the same disease haplotype, but the current patient lacks a homozygous variant present in the Irish siblings in the closely linked gene ZNF193, eliminating this as a contributor to the disease. The current patient also displays symptoms consistent with mitochondrial dysfunction, although levels of mitochondrial function in patient primary skin fibroblasts are normal. However, we demonstrate an inability in patient primary fibroblasts to rapidly repair topoisomerase-induced DNA double-strand breaks (DSBs) in the nucleus and profound hypersensitivity to this type of DNA damage.ConclusionsThese data confirm the TDP2 mutation as causative for SCAR23 and highlight the link between defects in nuclear DNA DSB repair, developmental delay, epilepsy, and ataxia.

APA, Harvard, Vancouver, ISO, and other styles

17

Pommier, Yves, Shar-yin N. Huang, Rui Gao, Benu Brata Das, Junko Murai, and Christophe Marchand. "Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2)." DNA Repair 19 (July 2014): 114–29. http://dx.doi.org/10.1016/j.dnarep.2014.03.020.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Li, Chunyang, Shi-Yong Sun, Fadlo R. Khuri, and Runzhao Li. "Pleiotropic functions of EAPII/TTRAP/TDP2." Cell Cycle 10, no. 19 (2011): 3274–83. http://dx.doi.org/10.4161/cc.10.19.17763.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

A.S., FILIMONOV, CHEPANOVA A.A., MIKHAILOVA M.A., et al. "SYNTHESIS OF THE NEW DERIVATIVES OF USNIC ACID AND STUDY OF THEIR INHIBITING ACTIVITY AGAINST TYROSYL-DNA-PHOSPHODIESTERASES 1 AND 2." Chemistry for Sustainable Development 31, no. 6 (2023): 698–706. http://dx.doi.org/10.15372/csd2023519.

Full text

Abstract:

Tyrosyl-DNA phosphodiesterases 1 and 2 (Tdp1 and Tdp2) are DNA repair enzymes that are considered as potential targets for antitumour supporting therapy in combination with topoisomerase inhibitors. The most effective Tdp1 inhibitors were found among the derivatives of the lichen secondary metabolite usnic acid. The sensitising effect of these compounds in combination with the topoisomerase 1 inhibitor topotecan was confirmed in cell culture experiments and animal models. In the present work, we describe new derivatives of usnic acid synthesized on the basis of previously obtained Tdp1 inhibitors by introducing the pyrazole cycle annelated with the C ring in dibenzofuran backbone, which makes it possible to reduce the intrinsic toxicity of the obtained compounds. New dual Tdp1 and Tdp2 inhibitors in the micromolar range of concentrations are found.

APA, Harvard, Vancouver, ISO, and other styles

20

Ribeiro, Carlos J. A., Jayakanth Kankanala, Jiashu Xie, Jessica Williams, Hideki Aihara, and Zhengqiang Wang. "Triazolopyrimidine and triazolopyridine scaffolds as TDP2 inhibitors." Bioorganic & Medicinal Chemistry Letters 29, no. 2 (2019): 257–61. http://dx.doi.org/10.1016/j.bmcl.2018.11.044.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Nitiss, John L., and Karin C. Nitiss. "Tdp2: A Means to Fixing the Ends." PLoS Genetics 9, no. 3 (2013): e1003370. http://dx.doi.org/10.1371/journal.pgen.1003370.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Marchand, Christophe, Monica Abdelmalak, Jayakanth Kankanala, et al. "Deazaflavin Inhibitors of Tyrosyl-DNA Phosphodiesterase 2 (TDP2) Specific for the Human Enzyme and Active against Cellular TDP2." ACS Chemical Biology 11, no. 7 (2016): 1925–33. http://dx.doi.org/10.1021/acschembio.5b01047.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

А.С., ФИЛИМОНОВ, ЗАХАРЕНКО А.Л., ЧЕПАНОВА А.А. та ін. "ИЗУЧЕНИЕ ИНГИБИРУЮЩЕЙ TDP1 И TDP2 СПОСОБНОСТИ И СЕНСИБИЛИЗИРУЮЩИХ ДЕЙСТВИЕ ПРОТИВООПУХОЛЕВЫХ ПРЕПАРАТОВ СВОЙСТВ НОВОГО ПРОИЗВОДНОГО УСНИНОВОЙ КИСЛОТЫ". Химия в интересах устойчивого развития 31, № 6 (2023): 728–36. http://dx.doi.org/10.15372/khur2023520.

Full text

Abstract:

Синтезировано новое производное усниновой кислоты, содержащее цианэтильный и изониазидный фрагменты. Соединение ингибирует активность фермента репарации ДНК Tdp1 со значением IC50 = 1.2 мкмоль/л, неактивно в отношении Tdp2 и не влияет на выживаемость клеток для панели пассируемых клеточных линий в диапазоне концентраций до 20 мкмоль/л. Показано, что соединение в комбинациях с определенными концентрациями противоопухолевых препаратов способно сенсибилизировать действие противоопухолевых препаратов олапариба и темозоломида на некоторых клеточных линиях. A new usnic acid derivative containing cyanethyl and isoniazid fragments is synthesised. The compound inhibits the activity of DNA repair enzyme Tdp1 with IC50 = 1.2 μM, is inactive against Tdp2 and does not affect cell survival for a panel of passaged cell lines in the concentration range up to 20 μM. It is shown that the compound in combinations with the certain concentrations of antitumour drugs can sensitise the effect of antitumour drugs olaparib and temozolomide on some cell lines.

APA, Harvard, Vancouver, ISO, and other styles

24

Zagnoli-Vieira, Guido, and Keith W. Caldecott. "TDP2, TOP2, and SUMO: what is ZATT about?" Cell Research 27, no. 12 (2017): 1405–6. http://dx.doi.org/10.1038/cr.2017.147.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Kiselev, Evgeny, Azhar Ravji, Jayakanth Kankanala, Jiashu Xie, Zhengqiang Wang, and Yves Pommier. "Novel deazaflavin tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors." DNA Repair 85 (January 2020): 102747. http://dx.doi.org/10.1016/j.dnarep.2019.102747.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Dyrkheeva, Nadezhda S., Aleksandr S. Filimonov, Olga A. Luzina, et al. "New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1." International Journal of Molecular Sciences 22, no. 21 (2021): 11336. http://dx.doi.org/10.3390/ijms222111336.

Full text

Abstract:

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3′ phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA–TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC50 values in the 1.4–25.2 μM range. The structure of the heterocyclic substituent introduced into the dibenzofuran core affects the TDP1 inhibitory efficiency of the compounds. A five-membered heterocyclic fragment was shown to be most pharmacophoric among the others. Sulfoxide derivatives were less cytotoxic than their thioester analogs. We observed an uncompetitive type of inhibition for the four most effective inhibitors of TDP1. The anticancer effect of TOP1 inhibitors can be enhanced by the simultaneous inhibition of PARP1, TDP1, and TDP2. Some of the compounds inhibited not only TDP1 but also TDP2 and/or PARP1, but at significantly higher concentration ranges than TDP1. Leader compound 10a showed promising synergy on HeLa cells in conjunction with the TOP1 inhibitor topotecan.

APA, Harvard, Vancouver, ISO, and other styles

27

Langereis, Martijn A., Qian Feng, Frank H. T. Nelissen, et al. "Modification of picornavirus genomic RNA using ‘click’ chemistry shows that unlinking of the VPg peptide is dispensable for translation and replication of the incoming viral RNA." Nucleic Acids Research 42, no. 4 (2013): 2473–82. http://dx.doi.org/10.1093/nar/gkt1162.

Full text

Abstract:

Abstract Picornaviruses constitute a large group of viruses comprising medically and economically important pathogens such as poliovirus, coxsackievirus, rhinovirus, enterovirus 71 and foot-and-mouth disease virus. A unique characteristic of these viruses is the use of a viral peptide (VPg) as primer for viral RNA synthesis. As a consequence, all newly formed viral RNA molecules possess a covalently linked VPg peptide. It is known that VPg is enzymatically released from the incoming viral RNA by a host protein, called TDP2, but it is still unclear whether the release of VPg is necessary to initiate RNA translation. To study the possible requirement of VPg release for RNA translation, we developed a novel method to modify the genomic viral RNA with VPg linked via a ‘non-cleavable’ bond. We coupled an azide-modified VPg peptide to an RNA primer harboring a cyclooctyne [bicyclo[6.1.0]nonyne (BCN)] by a copper-free ‘click’ reaction, leading to a VPg-triazole-RNA construct that was ‘non-cleavable’ by TDP2. We successfully ligated the VPg-RNA complex to the viral genomic RNA, directed by base pairing. We show that the lack of VPg unlinkase does not influence RNA translation or replication. Thus, the release of the VPg from the incoming viral RNA is not a prerequisite for RNA translation or replication.

APA, Harvard, Vancouver, ISO, and other styles

28

Shi, Ke, Kayo Kurahashi, Rui Gao, et al. "Structural basis for recognition of 5′-phosphotyrosine adducts by Tdp2." Nature Structural & Molecular Biology 19, no. 12 (2012): 1372–77. http://dx.doi.org/10.1038/nsmb.2423.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Gao, Rui, Shar-yin N. Huang, Christophe Marchand, and Yves Pommier. "Biochemical Characterization of Human Tyrosyl-DNA Phosphodiesterase 2 (TDP2/TTRAP)." Journal of Biological Chemistry 287, no. 36 (2012): 30842–52. http://dx.doi.org/10.1074/jbc.m112.393983.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

A.S., FILIMONOV, ZAKHARENKO A.L., CHEPANOVA A.A., et al. "STUDY OF THE ABILITY OF A NEW USNIC ACID DERIVATIVE TO INHIBIT TDP1 AND TDP2, AND SENSITISE THE EFFECT OF ANTITUMOUR DRUGS." Chemistry for Sustainable Development 31, no. 6 (2023): 707–14. http://dx.doi.org/10.15372/csd2023520.

Full text

Abstract:

A new usnic acid derivative containing cyanoethyl and isoniazid fragments is synthesised. The compound inhibits the activity of DNA repair enzyme Tdp1 with IC50 = 1.2 μM, is inactive against Tdp2 and does not affect cell survival for a panel of passaged cell lines in the concentration range up to 20 μM. It is shown that the compound in combinations with the certain concentrations of antitumour drugs can sensitise the effect of antitumour drugs olaparib and temozolomide on some cell lines.

APA, Harvard, Vancouver, ISO, and other styles

31

Habibagahi, Fatemeh, and Robert J. Crutchley. "Mixed-valence properties of a dinuclear ruthenium complex bridged by bis(phenylcyanamido)tetrazine." Canadian Journal of Chemistry 92, no. 11 (2014): 1081–85. http://dx.doi.org/10.1139/cjc-2014-0307.

Full text

Abstract:

The novel bridging ligand 3,6-bis(phenylcyanamido)-1,2,4,5-tetrazine (tdpcH2) and its dinuclear complex [{Ru(ttpy)(bpy)}2(μ-tdpc)][PF6]2 were prepared and characterized by elemental analysis and 1H NMR spectroscopy. Cyclic voltammetry and vis-NIR and IR spectroelectrochemistry of [{Ru(ttpy)(bpy)}2(μ-tdpc)]2+ showed that [{Ru(ttpy)(bpy)}2(μ-tdpc)]3+ is a Class II mixed-valence system with metal−metal coupling of 400 cm−1 assuming a transition dipole moment length of 21 Å. DFT calculations of tdpc2− suggested that the stability of the HOMO results in weak metal−metal coupling via the hole-superexchange mechanism.

APA, Harvard, Vancouver, ISO, and other styles

32

Kumagai, Hitoshi, Sadahiro Yagishita, Ken Kanazashi, et al. "Hydrogen-Bonding Assembly of Coordination Polymers Showing Reversible Dynamic Solid-State Structural Transformations." Inorganics 6, no. 4 (2018): 115. http://dx.doi.org/10.3390/inorganics6040115.

Full text

Abstract:

We herein report the synthesis, single-crystal structures of coordination polymers, and structural transformations of complexes employing 1,4,5,6-tetrahydro-5,6-dioxo-2,3-pyrazinedicarbonitrile (tdpd2−) and pyrazine (pyz) as bridging ligands. {[M(H2O)4(pyz)][M(tdpd)2(pyz)]·6(H2O)}n, [1·10H2O and 2·10H2O where M = Co (1) and Zn (2)], consists of two types of crystallographically independent one-dimensional (1D) structures packed together. One motif, [M(tdpd)2(pyz)]2− (A), is an anionic infinite pyz bridged 1D array with chelating tdpd2− ligands, and the other motif is a cationic chain, [M(H2O)4(pyz)]2+ (B), which is decorated with four terminal water molecules. The 1D arrays (A) and (B) are arranged in parallel by multi-point hydrogen-bonding interactions in an alternate (A)(B)(A)(B) sequence extending along the c-axis. Both compounds exhibit structural transformations driven by thermal dehydration processes around 350 K to give partially dehydrated forms, 1·2H2O and 2·2H2O. The structural determination of the partially dehydrated form, 2·2H2O, reveals a solid-state structural transformation from a 1D chain structure to a two-dimensional (2D) coordination sheet structure, [Zn2(tdpd)2(H2O)2(pyz)]n (2·2H2O). Further heating to 500 K yields the anhydrous form 2. While the virgin samples of 1·10H2O and 2·10H2O crystallize in different crystal systems, powder X-ray diffraction (PXRD) measurements of the dehydrated forms, 1·2H2O and 2·2H2O, are indicative of the same structure. The structural transformation is irreversible for 1·10H2O at ambient conditions. On the other hand, compound 2·10H2O shows a reversible structural change. The solid-state structural transformation for 1·10H2O was also confirmed by monitoring in-situ magnetic susceptibility, which is consistent with other thermally-induced measurements.

APA, Harvard, Vancouver, ISO, and other styles

33

Hall, Steven R., and Kerry Brennan Goralski. "ZATT, TDP2, and SUMO2: breaking the tie that binds TOP2 to DNA." Translational Cancer Research 7, S4 (2018): S439—S444. http://dx.doi.org/10.21037/tcr.2018.02.03.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Schellenberg, Matthew J., Lalith Perera, Christina N. Strom, et al. "Reversal of DNA damage induced Topoisomerase 2 DNA–protein crosslinks by Tdp2." Nucleic Acids Research 44, no. 8 (2016): 3829–44. http://dx.doi.org/10.1093/nar/gkw228.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Maciejewski, Sonia, Wendy Ullmer, and Bert L. Semler. "VPg unlinkase/TDP2 in cardiovirus infected cells: Re-localization and proteolytic cleavage." Virology 516 (March 2018): 139–46. http://dx.doi.org/10.1016/j.virol.2018.01.010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Kankanala, Jayakanth, Christophe Marchand, Monica Abdelmalak, Hideki Aihara, Yves Pommier, and Zhengqiang Wang. "Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2)." Journal of Medicinal Chemistry 59, no. 6 (2016): 2734–46. http://dx.doi.org/10.1021/acs.jmedchem.5b01973.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Gervas, P. A., A. Yu Molokov, N. N. Babyshkina, et al. "Whole exome sequencing: the search for mutations associated with hereditary breast cancer in ethnic groups of Siberia." Siberian journal of oncology 23, no. 5 (2024): 35–46. http://dx.doi.org/10.21294/1814-4861-2024-23-5-35-46.

Full text

Abstract:

Hereditary breast cancer (HBC) is a heterogeneous disease caused by mutations in genes characterized by ethnic specifcity. The clinical heterogeneity of this disease signifcantly complicates its diagnosis. The use of high-throughput sequencing is one of the approaches that allow the search for genes and their variants associated with the development of HBC. The purpose of the study was to search for new genes associated with HBC in the understudied ethnic groups of Siberia by using whole exome sequencing (WES).Material and Methods. WES was performed on a cohort of 16 probands with BC (Tuvan, Yakut, Altai ethnos). The study material was genomic DNA isolated from peripheral blood leukocytes. Libraries were prepared using a BGI Optimal DNA Library Prep kit. An Agilent SureSelect Human All Exon V6 kit was used for hybridization. High-throughput sequencing was performed on a DNA nanoball sequencing platform (DNBSeq-G400).Results. In the overall group of patients with signs of HBC, pathogenic variants were detected in 12.5 % of cases (2/16). For the frst time, BRCA1 (rs80357635) pathogenic variant was identified in a young patient with metachronous BC (Yakut ethnic group). A pathogenic variant of the ATM gene (rs780619951 NM_000051:exon16:c.C2413T:p.R805X) was identified in a young patient with BC (Tuvinian ethnic group). A pathogenic variant of the TDP2 c.G4T:p.E2X, rs770844602 gene (DNA repair gene) was identified for the frst time in a Tuvan BC patient (metachronous) with a family history, but its contribution to HBC remains to be proven. The TDG gene variant (rs764159587 NM_001363612:exon7:c.536dupA:p.E179fs) found in the Tuvan ethnic group and affecting splicing (SpliceAI: 0.580) requires special attention.Conclusion. This report is the frst to describe the germinal variant in the BRCA1 (rs80357635) gene in the Yakut ethnic group. Further studies are required to confrm pathogenicity of germinal variants in non-well studied genes TDP2, TDG in ethnic BC patients.

APA, Harvard, Vancouver, ISO, and other styles

38

Crampin, S., R. Evans, and S. B. Ucer. "Analysis of records of local earthquakes: the Turkish Dilatancy Projects (TDP1 and TDP2)." Geophysical Journal International 83, no. 1 (1985): 1–16. http://dx.doi.org/10.1111/j.1365-246x.1985.tb05152.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Bian, Ka, Naveen Reddy Muppani, Lobna Elkhadragy, et al. "ERK3 regulates TDP2-mediated DNA damage response and chemoresistance in lung cancer cells." Oncotarget 7, no. 6 (2015): 6665–75. http://dx.doi.org/10.18632/oncotarget.6682.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Zeng, Zhihong, Abhishek Sharma, Limei Ju, et al. "TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1." Nucleic Acids Research 40, no. 17 (2012): 8371–80. http://dx.doi.org/10.1093/nar/gks622.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Al Mahmud, Md Rasel, Kenichiro Ishii, Cristina Bernal‐Lozano, et al. "TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands." Genes to Cells 25, no. 7 (2020): 450–65. http://dx.doi.org/10.1111/gtc.12770.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Komulainen, Emilia, Lewis Pennicott, Darren Le Grand, and Keith W. Caldecott. "Deazaflavin Inhibitors of TDP2 with Cellular Activity Can Affect Etoposide Influx and/or Efflux." ACS Chemical Biology 14, no. 6 (2019): 1110–14. http://dx.doi.org/10.1021/acschembio.9b00144.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Gómez-Herreros, Fernando, Janneke H. M. Schuurs-Hoeijmakers, Mark McCormack, et al. "TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function." Nature Genetics 46, no. 5 (2014): 516–21. http://dx.doi.org/10.1038/ng.2929.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Yang, Hao, Xiao-Qing Zhu, Wenjie Wang, et al. "The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors." Bioorganic Chemistry 111 (June 2021): 104881. http://dx.doi.org/10.1016/j.bioorg.2021.104881.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Yu, Le-Mao, Zhu Hu, Yu Chen, et al. "Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2)." European Journal of Medicinal Chemistry 151 (May 2018): 777–96. http://dx.doi.org/10.1016/j.ejmech.2018.04.024.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Pahl, Paula, Ralph Berger, Iris Hart, Ho Zoom Chae, Sue Goo Rhee, and David Patterson. "Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent peroxide reductase gene (TPX), to chromosome 13q12." Genomics 26, no. 3 (1995): 602–6. http://dx.doi.org/10.1016/0888-7543(95)80183-m.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Li, Jinlin, Noemi Nagy, Jiangnan Liu, et al. "The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection." PLOS Pathogens 17, no. 9 (2021): e1009954. http://dx.doi.org/10.1371/journal.ppat.1009954.

Full text

Abstract:

Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2cc), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell line carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2cc debulking that favors cell survival and virus production.

APA, Harvard, Vancouver, ISO, and other styles

48

Ribeiro, Carlos J. A., Jayakanth Kankanala, Ke Shi, et al. "New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2)." European Journal of Pharmaceutical Sciences 118 (June 2018): 67–79. http://dx.doi.org/10.1016/j.ejps.2018.03.021.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Tang, Lu, Nora Fung-Yee Tam, Winnie Lam, Thomas Chun-Hung Lee, Steven Jing-Liang Xu, and Fred Wang-Fat Lee. "Insights into Nitrogen-Associated Protein 50 (NAP50) as a Tyrosyl–DNA Phosphodiesterase in Dinoflagellates." Microorganisms 12, no. 11 (2024): 2286. http://dx.doi.org/10.3390/microorganisms12112286.

Full text

Abstract:

Nitrogen-associated protein 50 (NAP50) is an abundant plastid protein with an unknown function identified in Alexandrium affine (Dinophyceae). No progress has been made in discovering the function of NAP50 since its first characterization in 2009. The present study is a continuation of work on the predicted function of NAP50. The results show that the NAP50 gene lacks introns but contains abundant base substitutions, consistent with the characteristics of dinoflagellate nuclear genes. The NAP50 protein is found to be widely expressed in dinoflagellate lineages through bioinformatics analysis and Western blotting, suggesting that NAP50 is not exclusive to Alexandrium, which differs from previous understandings. Phylogenetic analysis reveals that NAP50 belongs to the tyrosyl–DNA phosphodiesterase (TDP) family; however, it is structurally distinct from the TDP2 that is present in some dinoflagellate species. The three-dimensional structure and biological functions of NAP50 are predicted using deep learning algorithms. Based on evolutionary relationships and functional predictions, NAP50 may play a role in repairing plastid DNA damage and potentially contribute to the transcription of plastid genes in dinoflagellates.

APA, Harvard, Vancouver, ISO, and other styles

50

Morimoto, Tsuda, Bunch, Sasanuma, Austin, and Takeda. "Type II DNA Topoisomerases Cause Spontaneous Double-Strand Breaks in Genomic DNA." Genes 10, no. 11 (2019): 868. http://dx.doi.org/10.3390/genes10110868.

Full text

Abstract:

Type II DNA topoisomerase enzymes (TOP2) catalyze topological changes by strand passage reactions. They involve passing one intact double stranded DNA duplex through a transient enzyme-bridged break in another (gated helix) followed by ligation of the break by TOP2. A TOP2 poison, etoposide blocks TOP2 catalysis at the ligation step of the enzyme-bridged break, increasing the number of stable TOP2 cleavage complexes (TOP2ccs). Remarkably, such pathological TOP2ccs are formed during the normal cell cycle as well as in postmitotic cells. Thus, this ‘abortive catalysis’ can be a major source of spontaneously arising DNA double-strand breaks (DSBs). TOP2-mediated DSBs are also formed upon stimulation with physiological concentrations of androgens and estrogens. The frequent occurrence of TOP2-mediated DSBs was previously not appreciated because they are efficiently repaired. This repair is performed in collaboration with BRCA1, BRCA2, MRE11 nuclease, and tyrosyl-DNA phosphodiesterase 2 (TDP2) with nonhomologous end joining (NHEJ) factors. This review first discusses spontaneously arising DSBs caused by the abortive catalysis of TOP2 and then summarizes proteins involved in repairing stalled TOP2ccs and discusses the genotoxicity of the sex hormones.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!