Breast cancer predisposition gene brca1, pathogenic c61g mutation in mice: synthetic viability in DNA repair and tumour development

[摘要] The N-terminus of BRCA1 is clinically important as inheritance of a mutation in this region correlates to an increased risk is breast and ovarian cancer. Whilst this is fairly clear, what specific mutations do and the aetiology of the disease is not clear.This thesis investigates N-terminal BRCA1 mutations using both \(in\) \(vitro\) and cell-based methods with a focus on DNA repair, mainly double-strand break and DNA crosslink repair. The use of chemotherapy agents is used with specific mutations to look at the individual phenotypes these create to each drug or radiation. This thesis also provides evidence on haploinsufficient or dominant negative effects of N-terminal mutations.Overall, the N-terminus of BRCA1 can affect DNA repair and increase genome instability that may lead to tumour development.

[发布机构] University:University of Birmingham;Department:Institute of Cancer Studies

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)