Date of Award
8-2014
Document Type
Thesis
Degree Name
Master of Science (MS)
Legacy Department
Biochemistry and Molecular Biology
Committee Member
Dr. Michael G. Sehorn, Committee Chair
Committee Member
Dr. William R. Marcotte, Jr.
Committee Member
Dr. Kerry S. Smith
Committee Member
Dr. Meredith T. Morris
Abstract
DNA double strand breaks (DSB) are the most genotoxic lesions because they affect the integrity of the genome. DSBs can be caused by exogenous factors such as ionizing radiation or induced during meiosis. Failure to repair DSBs can cause genome instability, cancer and cell death. DSBs can be repaired by one of three main pathways, homologous recombination (HR), non-homologous end joining (NHEJ) and microhomology mediated end joining (MMEJ). NHEJ and MMEJ are error-prone but HR is relatively error-free since it relies on a homologous DNA sequence. Studies have shown that HR accounts for repair of about 50% of induced DSBs. HR is also essential for proper segregation of chromosomes and telomere maintenance in eukaryotes. Impaired HR is implicated in diseases like Bloom’s syndrome, Fanconi’s anemia and breast and ovarian cancer. In eukaryotes, the mechanism of HR is largely governed by two recombinases, Rad51 and Dmc1, the homologs of E. coli RecA. Dmc1 is meiosis-specific whereas Rad51 functions in mitosis and meiosis. Rad51 and Dmc1 mediate ATP-dependent DNA strand exchange and require recombination mediators and accessory factors to assist them in forming a presynaptic filament on single-stranded DNA and search for homology. This study involved examining the biochemical properties of a set of proteins with respect to their function in RAD51-mediated homologous recombination. The results indicated that HELLS, BCCIPα and BCCIPβ interact with RAD51 and bind single-stranded DNA. Further, these proteins function in HR by stabilizing the RAD51 presynaptic filament and preventing it from dissociation, thus promoting efficient recombination.
Recommended Citation
Shah, Shivani B., "Understanding the Role of Regulators of Homologous Recombination" (2014). All Theses. 2501.
https://open.clemson.edu/all_theses/2501