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Dissertations / Theses on the topic 'Checkpoint'

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1

Ho, Chui Chui. "Characterization of the regulation of p53 and checkpoint kinases in DNA integrity checkpoints /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BICH%202006%20HO.

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2

Liang, Hongqing. "Quantitative analysis of interactions between cell cycle kinases and checkpoint pathways during checkpoint recovery." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607913.

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3

Wang, Kexi. "Silencing of the Mitotic Checkpoint." University of Toledo / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1410369908.

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4

Ji, Wenbin. "Regulation of the Mitotic Checkpoint." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1484174079006341.

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5

Smoler, Gunilla Kanter. "Functional characterization of conserved checkpoint genes." Göteborg, Sweden : Dept. of Cellular and Molecular Biology, Göteborg University, 1998. http://books.google.com/books?id=vM5qAAAAMAAJ.

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6

Mirchenko, L. "Mitotic checkpoint inactivation at anaphase onset." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1302282/.

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The mitotic checkpoint prevents chromosome segregation until all chromosomes have reached bi-polar orientation and come under tension on the mitotic spindle. Once this is achieved, the protease separase is activated to cleave the chromosomal cohesin complex and trigger anaphase. Cohesin cleavage releases tension between sister chromatids, however the mitotic checkpoint fails to respond to this apparent tension defect. The aim of this study was to understand why the mitotic checkpoint remains silent when sisters lose tension due to cohesin cleavage in anaphase. We showed in budding yeast that l
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7

Kanter, Smoler Gunilla. "Functional characterisation of conserved checkpoint genes." Göteborg : [s.n.], 1998. http://catalog.hathitrust.org/api/volumes/oclc/45150869.html.

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8

Yuan, Ivan. "Generation of synthetic spindle checkpoint signals." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22030.

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The spindle checkpoint ensures proper chromosome segregation by monitoring kinetochore-microtubule interactions: unattached kinetochores recruit checkpoint proteins that combine to form a diffusible inhibitor which delays anaphase, thus buying cells time to fix attachment errors. Although the major checkpoint proteins were identified some 25 years ago, we have only just begun to understand how they assemble at unattached kinetochores to generate the crucial checkpoint signal. Much of this can be attributed to the difficulty associated with studying these proteins at the kinetochores, which are
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9

On, Kin Fan. "The role of MAD2L1BP in the silencing of the spindle-assembly checkpoint and the DNA damage checkpoint /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?BICH%202009%20ON.

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10

Weirich, Alexandra. "Initiating the Spindle Assembly Checkpoint Signal: Checkpoint Protein Mad1 Associates with Outer Kinetochore Protein Ndc80 in Budding Yeast." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24248.

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The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism that delays the initiation of anaphase by inhibiting the Anaphase Promoting Complex (APC) until all kinetochores have achieved bipolar attachment on the mitotic spindle. Mad1-3, Bub1, and Bub3, components of the SAC, are conserved from yeast to humans. These proteins localize to unattached kinetochores, though it is unknown with which kinetochore proteins they interact and how these interactions transduce information about microtubule attachement. Here, purification of the checkpoint proteins from Saccharomyces ce
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Savatovic, Anita, and Mejra Cakic. "Estimating Optimal Checkpoint Intervals Using GPSS Simulation." Thesis, Linköping University, Department of Mathematics, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8558.

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<p>In this project we illustrate how queueing simulation may be used to find the optimal interval for checkpointing problems and compare results with theoretical computations for simple systems that may be treated analytically.</p><p>We consider a relatively simple model for an internet banking facility. From time to time, the application server breaks down. The information at the time of the breakdown has to be passed onto the back up server before service may be resumed. To make the change over as efficient as possible, information of the state of user’s accounts is saved at regular interval
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12

Sen, Onur. "Phospho-regulation of the spindle assembly checkpoint." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/15873.

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Mitosis is a highly regulated process by which a cell duplicates and distributes its chromosomal DNA into two identical daughter cells equally. Equal distribution of the chromosomes is crucial for accurate propagation of genetic information. This is essential for maintaining viability and preventing genomic instability that can potentially lead to cancer. In order to avoid unequal distribution of chromosomes, cells employ a surveillance mechanism called the spindle assembly checkpoint (SAC). The SAC is an inhibitory signalling network, which delays segregation of chromosomes, until they have s
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13

Jeganathan, Karthik Babu. "The mitotic checkpoint: mechanism and biological relevance." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/.

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14

McAllister, Roisin. "Mitotic checkpoint responses in Chinese hamster cells." Thesis, University of Ulster, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588491.

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The mitotic spindle checkpoint is a constitutively active mechanism that protects cells from aneuploidy. Cell lines exhibit variable capacities to activate this checkpoint and rodent cells, such as CHO-K1, are well known to possess a less stringent checkpoint than human cells. Preliminary analysis of a panel of CHO-K1-human chromosome somatic cell hybrids, identified 15A (retaining human chromosome 15) as having an augmented checkpoint. Reanalysis of the two cell lines here, using both microscopy and flow cytometry, found 15A to have a higher mitotic index during an unperturbed cell cycle; but
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15

Hutter, Lukas Hermann. "Systems-level analysis of the mitotic checkpoint." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:19b5ae63-f310-4a9d-8927-41088287514f.

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The mitotic checkpoint regulates a critical transition in the eukaryotic cell cycle. It delays exit from mitosis until all chromosomes have become bi-oriented. In spite of an impressive body of work uncovering mechanistic aspects of the mitotic checkpoint, a detailed understanding of how the mitotic checkpoint operates as a control system continues to evade us. Here, I present three systems-biological studies aimed at elucidating distinct aspects of the mitotic checkpoint control system. Using a combination of dedicated experiments and mathematical modelling, we investigate the fragile respons
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Conde, Rui Miguel Esteves Antunes Seabra. "Protein phosphatases acting on the replication checkpoint." Doctoral thesis, Universidade de Aveiro, 2010. http://hdl.handle.net/10773/3494.

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Doutoramento em Biologia<br>A génese de um cancro está dependente da acumulação de mutações genéticas que dão origem a instabilidade genómica, que por sua vez resulta na proliferação descontrolada. Para prevenir a acumulação destas mutações, as células têm mecanismos de controlo (checkpoints) que suspendem o ciclo celular e accionam as vias de reparação do ADN. Estes eventos são muitas vezes regulados por dinâmicas de (des)fosforilação de proteínas. As proteínas fosfatases (PPs), enzimas responsáveis pela remoção do grupo fosfato de resíduos fosforilados, desempenham funções cruciais na
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Nevis, Kathleen Rae Cordeiro-Stone Marila Cook Jeanette G. "Molecular characterization of a replication licensing checkpoint." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2009. http://dc.lib.unc.edu/u?/etd,2426.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2009.<br>Title from electronic title page (viewed Sep. 3, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pathology and Laboratory Medicine." Discipline: Pathology and Laboratory Medicine; Department/School: Medicine.
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18

Little, Elizabeth J. "DNA damage sensors in the checkpoint response." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/289950.

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The DNA damage checkpoint response detects DNA damage and responds to the damage by promoting DNA repair, transcriptional regulation, and cell cycle arrest. Prior to the beginning of this dissertation the checkpoint sensor proteins in S. cerevisiae were identified as Ddc1, Mec3, Rad9, Rad17 and Rad24. However, none of the sensors had been shown to bind DNA directly, an anticipated function of checkpoint sensors. To characterize these proteins a biochemical approach was taken to test whether any of the checkpoint sensor proteins could detect DNA. The associated DNA binding properties of Rad24 a
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19

Hewitt, Laura. "Using a novel small molecule inhibitor to investigate the role of Mps1 kinase activity." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/using-a-novel-small-molecule-inhibitor-to-investigate-the-role-of-mps1-kinase-activity(fcacfefc-90d9-4e92-9af4-a57897737329).html.

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During mitosis, accurate chromosome segregation is essential: gain or loss of genetic information can be detrimental to cell viability, or promote tumourigenesis. The mitotic checkpoint (also known as the spindle assembly checkpoint or SAC) ensures accurate chromosome segregation by delaying cell cycle progression until accuracy can be guaranteed. Mps1 is a protein kinase that is crucial for mitotic checkpoint signalling and also for proper chromosome alignment at metaphase. However, the precise role of Mps1’s catalytic activity is still unclear. Here, I present AZ3146, a novel small molecule
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20

Zhou, Yan. "Regulation of Aurora A activity during checkpoint recovery." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181746.

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Cell division requires accurate DNA replication and cells develop checkpoint mechanisms toensure the correct passage of the genetic material. Cells arrest by a checkpoint when DNAdamage is found. After the checkpoint is silenced, the cell cycle can be resumed. Polo-likekinase 1 (Plk1) and Aurora A kinase (AurA) are both important regulators for checkpointrecovery. The question how AurA is activated was studied by many researchers, but the exactmechanism stays unclear.We developed a new setup to study AurA activation during checkpoint recovery. Quantitativeimmunofluorescence of fixed cells as w
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21

Fersht, N. "The checkpoint role of Cdc18 in fission yeast." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445447/.

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The highly conserved eukaryotic checkpoints keep tight control over cell cycle progression, arresting the cell in response to incomplete DNA replication or DNA damage. In fission yeast, Rad3 (functional homologue of ATM, mutated in ataxia telangiectasia, and structural homologue of ATR, ataxia telangiectasia and rad3 related) is necessary for activation of both replication and damage checkpoints. However, despite the identification of many checkpoint genes, the actual sequence of upstream events leading to Rad3 activation remains unclear. The aim of my project was to identify and characterise
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22

Martinho, Rui Goncalo V. R. C. "Analysis of Rad3 and Chk1 checkpoint protein kinases." Thesis, University of Sussex, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297946.

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23

Leontiou, Ioanna. "'SynCheck' : new tools for dissecting Bub1 checkpoint functions." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33246.

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The accurate segregation of DNA during cell division is essential for the viability of future cellular generations. Genetic material is packaged in the form of chromosomes during cell division, and chromosomes are segregated equally into two daughter cells. Chromosome mis-distribution leads to genetic disorders (e.g. Down's syndrome), aneuploidy and cancer. The spindle checkpoint ensures proper chromosome segregation by monitoring kinetochore-microtubule interactions. Upon checkpoint activation, unattached kinetochores recruit checkpoint proteins that combine to form a diffusible inhibitor (th
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24

Smith, Joanne Louise. "Role of checkpoint kinase 1 in malignant melanoma." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4048/.

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Chk1 is a conserved protein kinase which is activated in response to multiple exogenous and endogenous genotoxic stresses. In response Chk1 mediates several cell cycle checkpoint responses which are important components of the cellular DNA damage response (DDR) pathway and as such are important in maintaining genome integrity throughout the cell cycle. The aim of this study was to investigate the potential role that Chk1 may play in the maintenance and progression of malignant melanoma using both in vitro and in vivo models; and to determine if Chk1 inhibition could be a viable therapeutic app
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25

Dodson, Helen. "Analysis of the spindle assembly checkpoint in vertebrates." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/13671.

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I have cloned the chicken <i>BubR1</i> cDNA and raised antibodies to the protein. The protein is highly conserved when compared to other vertebrate BubR1s with 55% identity and 70% similarity to human. The antibody recognises a protein of approximately 150 kDa and stains the kinetochores of chicken cells during prometaphase with the signal disappearing as they become attached to microtubules, a localisation typical of spindle checkpoint proteins. In order to further characterise the function of this protein in vertebrates, I have attempted to generate a chicken DT40 cell line conditionally nul
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26

Tipton, Aaron R. "How to Assemble a Functional Mitotic Checkpoint Complex." University of Toledo / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1341597834.

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27

Nahar, Kazi Jannatun. "Mechanisms of immune checkpoint inhibitor-induced gastrointestinal toxicities." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29500.

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Monoclonal antibodies against immune checkpoints such as CTLA-4 and PD-1/PD-L1 have improved response and survival outcomes in advanced melanoma. While improving anti-tumour responses, they can also give rise to atypical inflammatory side effects known as immune-related adverse events (irAEs). Gastrointestinal irAEs, mainly colitis can lead to significant morbidity and cessation of treatment. It is important to identify characteristics and potential mechanisms of colitis to guide treatments without compromising their outcomes. Therefore, the thesis aimed to define the characteristics of coliti
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28

Stephens, Peter Andrew. "An evaluation of the checkpoint kinase inhibitor V158411." Thesis, University of Newcastle upon Tyne, 2015. http://hdl.handle.net/10443/2957.

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The aim of this work was to characterise the checkpoint 1 kinase (CHK1) inhibitor V158411; its effect on DNA damage-induced checkpoint function in parallel with chemo/radio-potentiation in a panel of cell lines characterised for their CHK1 expression and activity. Furthermore, to determine the single agent cytotoxicity in a panel of cell lines; to identify potential pharmacodynamic biomarkers of CHK1 activity suitable for measuring the activity of inhibitors in the clinic; and to explore the role of p53 and identify other potential determinants of sensitivity to CHK1 inhibitors. V158411 on its
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29

Gardner, Richard Donald 1967. "Defining response pathways of budding yeast checkpoint genes." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282722.

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Cell cycle events are ordered correctly; mitosis follows DNA replication. To ensure correct order, cells employ checkpoints that delay the cycle when DNA replication, repair, or spindle assembly have not been completed. In this dissertation, I have focused on the DNA damage checkpoint, which arrests the cell in G₂ in response to DNA damage (the G₂/M checkpoint). I have studied the roles of several checkpoint genes in the budding yeast Saccharomyces cerevisiae involved in the response to DNA damage, focusing on a key gene called MEC1. I have tested genetically where in several pathways checkpoi
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Dutta, Chaitali. "Checkpoint Regulation of S-Phase Transcription: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/391.

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The DNA replication checkpoint transcriptionally up-regulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF (aka DSC1), the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitrophosp
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Roca, Marianne. "The spindle assembly checkpoint in Phallusia mammillata embryos." Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS500.

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Le point de contrôle du fuseau mitotique (Spindle Assembly Checkpoint : SAC) retarde l’anaphase jusqu’à ce que tous les chromosomes soient attachés correctement aux microtubules. Le SAC permet ainsi d’éviter des erreurs de ségrégation des chromosomes aboutissant à des cellules filles aneuploïdes (i.e. avec un nombre anormal de chromosomes). L’aneuploïdie, délétère pour les cellules, peut entrainer des problèmes de développement et est observée dans les cancers. Cependant, chez certaines espèces, le SAC n’est pas efficace au cours de la phase précoce du développement embryonnaire. J’ai mis en é
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Putnam, Charles Wellington. "Integration of G2/M checkpoint, spindle assembly checkpoint,and Ran cycle regulators in the Saccharomyces cerevisiae DNA damage mitotic arrest response." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280738.

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It is axiomatic that genomic stability is dependent upon regulatory pathways, termed checkpoints, which sense perturbations of cell cycle execution including damage to chromosomal DNA. In Saccharomyces cerevisiae, the principal DNA damage checkpoint is at G2/M. Heretofore, this and other checkpoints, such as the spindle assembly checkpoint, which is also operative at the metaphase/anaphase transition, have been viewed as essentially linear pathways, responding to a specific type of damage, signaling via sui generis proteins, and targeting a limited number of effectors for arrest. In a 1999 rep
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Paderi, Francesca. "Checkpoint protein Rad9 participates in Rhp18 specific PRR pathway, and physically interacts with ssDNA binding protein RPA as a pre-checkpoint complex." Thesis, University of Sussex, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508973.

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Pansani, Fabianna. "Expressão imunohistoquímica do Chk2 e associação com características clínico-patológicas e desfecho em pacientes com câncer de cólon metastático." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17154/tde-15062015-090143/.

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INTRODUÇAO: O câncer de cólon é a terceira neoplasia mais prevalente no país, com aumento progressivo da incidência associada ao envelhecimento populacional. Os avanços nos tratamentos local e sistêmico do câncer de cólon metastático tem aumentado significativamente o tempo de sobrevida global. Entretanto, ainda não existem biomarcadores consolidados na literatura, capazes de predizer resposta a estes tratamentos ou o prognóstico. No processo da carcinogênese, uma das importantes vias que se encontra alterada é a via de reparo do DNA. A Chk2 é uma proteína quinase com atividade no reparo celul
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Lund, Ingunn, and Anja Karense Lønningen. "Referanseimplementering av Checkpoint Service API ved bruk av Heartbeat." Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2005. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-10205.

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<p>Det eksisterer per i dag ingen implementasjon av standard grensesnitt for å tilby høytilgjengelige systemer i kombinasjon med standard maskinvareplattformer, mellomvare og tjenesteapplikasjoner. Dette medfører at programvaren må tilpasses ulike plattformer og ressurser som er tilgjengelige. Individuell tilpasning resulterer i økte kostnader og tidsforbruk, samt større usikkerhet i forbindelse med utvikling. Service Availibilty Forum presenterer Application Interface Specification (AIS) som er et standard grensesnitt for høytilgjengelige løsninger. Rapporten beskriver en prøveimplementasjon
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Kirkeby, Håkon. "In silico Investigation of Possible Mitotic Checkpoint Signalling Mechanisms." Thesis, Norwegian University of Science and Technology, Department of Mathematical Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9663.

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<p>The mitotic checkpoint is the major bio-chemical pathway acting to ensure stable genome content in cell division. A delay in chromosome segregation is enforced as long as at least one kinetochore is in lack of proper attachment to the mitotic spindle, something that prevents premature initiation of anaphase and uneven chromosome distribution. The backbone of the mitotic checkpoint control system is established as the production of a wait-anaphase signal at the unattached kinetochores. However, how this signal is able to support a functional checkpoint is unclear. To explore the performance
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Yin, Ling. "Activation of DNA Replication Initiation Checkpoint in Fission Yeast." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/194.

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In the fission yeast, Schizosacchromyces pombe, blocks to DNA replication elongation trigger the intra-S phase checkpoint that leads to the activation of the Cds1 kinase. Cds1 is required to both stabilize stalled replication forks and to prevent premature entry into mitosis. Interestingly, although Cds1 is essential to maintain the viability of mutants defective in DNA replication elongation, my study shows that mutants defective in DNA replication initiation require the Chk1 kinase, rather than Cds1. This suggests that failed initiation events can lead to activation of the DNA damage checkpo
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Tarailo, Maja. "Spindle assembly checkpoint and chromosome stability in Caenorhabditis elegans." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/5587.

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In many species, proper chromosome segregation is accomplished with the aid of a surveillance mechanism, the spindle assembly checkpoint. To identify the mechanisms involved in this process, the mutants that suppress or enhance the mdf-1(gk2)/MAD1 checkpoint lethality were characterized. The suppressors of mdf-1 (gk2) fall into two classes. The major class of suppressors compensates for the loss of the checkpoint by delaying mitotic progression. This class includes two known suppressors and anaphase promoting complex/cyclosome (APC/C) components, emb-30/APC4 and fzy-1/CDC2O, and four new such
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Chan, Steven 1980. "A semantic checkpoint framework for enabling runtime-reconfigurable applications." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/28475.

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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.<br>Includes bibliographical references (p. 81-82).<br>This thesis proposes to enable runtime-reconfigurable applications through the use of semantic checkpointing. We view applications here as a collection of inter-connected components, and reconfigurations as the reconstitution of components that make up an application. By checkpointing only values that are deemed to be of semantic significance, application state is maintained across reconfigurations even if the two configurati
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Cruz, Nelly Marie. "Identification of TICRR, a novel checkpoint and replication regulator." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/65290.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011.<br>Cataloged from PDF version of thesis. Page 141 blank.<br>Includes bibliographical references.<br>The eukaryotic cell cycle refers to a sequence of events by which a cell duplicates its genomic DNA and divides into two daughter cells. Deregulation of the cell cycle can cause aberrant cell proliferation, as well as genomic and chromosomal instability, events that contribute to the development of cancer. Along with the machinery that promotes cell cycle progression, cells have evolved surveillance mechanisms, or ch
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Hagan, Robert S. "Regulation of the spindle checkpoint by Mad2 binding proteins." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/33756.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.<br>Includes bibliographical references.<br>The spindle checkpoint ensures the fidelity of chromosome segregation by delaying anaphase until all sister chromatids form proper bipolar attachments to the mitotic spindle. Spindle checkpoint proteins localize to unattached or maloriented kinetochores in mitosis and generate a signal that prevents dissolution of sister chromatid cohesion. Checkpoint signaling requires binding of Mad2 to the checkpoint protein Madl and Cdc20, a subunit of the Anaphase Promoting Complex. W
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Searle, Jennifer. "The Role of PKA in the DNA Damage Checkpoint." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123003066.

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43

Kiser, Gretchen Louise. "Cell cycle checkpoint control in budding yeast Saccharomyces cerevisiae." Diss., The University of Arizona, 1995. http://hdl.handle.net/10150/187074.

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Multiple checkpoint controls ensure that later cellular events are not initiated until previous cellular events have been successfully completed. Our laboratory studies the checkpoint at the G2/M boundary that ensures the integrity of chromosome transmission by blocking mitosis until DNA synthesis and repair is completed. The checkpoint-dependent cell division arrest is one of several prominent responses to DNA damage, which also includes transcriptional induction of damage-inducible genes and DNA repair. I undertook three projects that explore several aspects of the damage response: (1) I fur
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Bianco, Julien. "Rôle du complexe Claspine-Timeless-Tipin dans le maintien de la stabilité du génome au cours de la réplication." Thesis, Montpellier 1, 2010. http://www.theses.fr/2010MON1T009/document.

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Il a été montré récemment que l'instabilité génétique joue un rôle central dans les étapes précoces de la tumorigenèse. Celle-ci provoquerait une activation chronique des voies ATR/CHK1 et ATM/CHK2 dans les cellules précancéreuses, entrainant l'apoptose ou la sénescence des cellules concernées. Les mécanismes de checkpoint constituant une barrière contre la progression tumorale, toute mutation affectant ce checkpoint serait ainsi sélectionnée très tôt dans le processu s de tumorigenèse et faciliterait ensuite la progression tumorale. Ce modèle met en évidence le rôle central de l'instabilité g
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Leau, Raphaëlle. "Engagement de CD28H : opportunité de stimulation et défis liés à l’expression de HHLA2." Electronic Thesis or Diss., Nantes Université, 2024. http://www.theses.fr/2024NANU1019.

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Dans un contexte où les immunothérapies ont révolutionné le traitement des cancers, certains patients demeurent réfractaires, soulignant la nécessité de découvrir de nouvelles cibles thérapeutiques. Cette thèse traite de l’étude de CD28H, un récepteur activateur dont le ligand, HHLA2, faiblement exprimé par les cellules épithéliales, suscite un intérêt croissant en raison de sa surexpression dans de nombreux cancers. Ma thèse explore la possibilité de cibler CD28H, afin de développer de nouvelles stratégies thérapeutiques d’une part et traite des conséquences de l’engagement de CD28H à son lig
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46

Mangsbo, Sara. "Immunological Checkpoint Blockade and TLR Stimulation for Improved Cancer Therapy." Doctoral thesis, Uppsala universitet, Enheten för klinisk immunologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110147.

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This thesis concerns the investigation of novel immunotherapies for cancer eradication. CpG therapy was used in order to target antigen-presenting cells (APCs), facilitating antigen presentation and activation of T cells. Blockade of the two major immune checkpoint regulators (CTLA-4 and PD-1) was also studied to ensure proper and sustained T cell activation. The therapies were investigated alone and compared to BCG, the standard immunotherapy in the clinic today for bladder cancer. In addition, CpG as well as BCG was combined with CTLA-4 or PD-1 blockade to examine if the combination could im
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Boyes, Laura. "Investigating the role of spindle checkpoint mutations in colorectal cancer." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/25352.

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It has been hypothesised that mutations in genes involved in chromosome segregation and mitotic checkpoints may contribute to aneuploid phenotypes in colon tumours. In support of this hypothesis deletions and missense mutations in spindle checkpoint genes <i>BUB1</i> and <i>BUBR1</i> have previously been reported in non-diploid colon cancers with defective mitotic checkpoints which also display chromosomal instability. We identified a deleted <i>BUBR1</i> transcript in 25% of a panel of aneuploid colorectal tumours from young patients. The deletion, termed DE5, removes a protein domain that is
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Johnson, Mary Kathrine. "THE METAPHASE CHECKPOINT IN CELLS UNDERGOING MITOSIS WITHOUT CHROMOSOME DUPLICATION." MSSTATE, 2007. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07062007-115810/.

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Chinese hamster ovary cells (CHO) were arrested with hydoxyurea at the beginning of DNA synthesis. Subsequent treatment with caffeine induced cells to bypass S-phase and undergo mitosis with unreplicated genomes (MUG). Treated cells built a normal spindle and distributed unattached kinetochores to daughter cells. To determine if MUG cells obey the metaphase checkpoint, we used immunoflourescence to detect and localize known metaphase checkpoint and motor proteins. In addition, the drug taxol was used to stabilize microtubules in MUG cells. The localization of CENP- E, the presence of anaphase
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Gastwirt, Randy Francis. "Spy1 regulation of the cell cycle, checkpoint activation and apoptosis." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3291605.

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Thesis (Ph. D.)--University of California, San Diego, 2008.<br>Title from first page of PDF file (viewed March 17, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Hsieh, Hsiang Chuan. "Checkpoint modulation of T cell immunity by novel fusion cytokines." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121154.

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Functional immunity requires a balanced T cell immune response, which entails the maintenance of de novo production (i.e. TCR repertoire diversity) and the appropriate differentiation of effector subsets at the periphery. However, numerous pathogenic changes can perturb this homeostasis. On the one hand, diminished thymopoiesis or exhausted effectors cause immune dysfunction, leading to the persistence of virally infected or cancerous cells. Unrestrained immune reaction, on the other hand, can cause significant tissue damage. The main objective of my thesis therefore was to develop novel thera
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