The role of the sister chromatid during repair of a DNA double-strand break
File(s)
Author(s)
Patel, A
Type
Thesis
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.
Version
Open Access
Editor(s)
Aragon, L
Date Issued
2014-05-01
Date Awarded
2014-05
Citation
2014
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Aragon, Luis
Sponsor
Medical Research Council (Great Britain)
Imperial College London
National Institute for Health Research (Great Britain)
Imperial College Healthcare NHS Trust
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)