Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.684234
Title: The role of the sister chromatid during repair of a DNA double-strand break
Author: Patel, Amit
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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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.
Supervisor: Aragon, Luis Sponsor: Medical Research Council ; Imperial College London ; National Institute for Health Research ; Imperial College Healthcare NHS Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.684234  DOI: Not available
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