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The role of the sister chromatid during repair of a DNA double-strand break

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Title: The role of the sister chromatid during repair of a DNA double-strand break
Authors: Patel, Amit
Item Type: Thesis or dissertation
Abstract: Chromosomal breaks are extremely cytotoxic and can occur during normal cell metabolism, and after exposure to exogenous DNA damaging agents. Double strand breaks (DSBs) are repaired to maintain and restore genetic integrity, principally through two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). HR can be error-free when sister chromatids are used as a template for repair, and is initiated by nucleolytic resection of the DSB. Cyclin-dependent kinase 1 (Cdk1) activity is crucial to promote HR. As Cdk1 activity and the sister chromatid are only present during certain cell division cycle stages, this study investigated whether in addition to Cdk1 activity the presence of an intact sister chromatid is a requirement to initiate HR. Conditional alleles that arrest the cell division cycle with separated sister chromatids and high Cdk1 activity were constructed in budding yeast and used to investigate this possibility. This study has found that HR occurs with segregated sister chromatids during telophase, at a time when mitotic Cdk1 activity is high. HR is also less efficient during metaphase if microtubule function is impaired. Overall, the availability of the sister chromatid is not an additional requirement to mitotic Cdk1 activity to promote DSB repair with the HR pathway.
Content Version: Open Access
Issue Date: Sep-2013
Date Awarded: May-2014
URI: http://hdl.handle.net/10044/1/32101
DOI: https://doi.org/10.25560/32101
Supervisor: Aragon, Luis
Sponsor/Funder: Medical Research Council (Great Britain)
Imperial College London
National Institute for Health Research (Great Britain)
Imperial College Healthcare NHS Trust
Department: Department of Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses



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