Date of Award

8-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biochemistry and Molecular Biology

Committee Chair/Advisor

Michael Sehorn

Committee Member

Jennifer Mason

Committee Member

Kimberly Paul

Committee Member

Meredith Morris

Abstract

Meiosis is a specialized form of cell division that produces cells containing a haploid number of chromosomes. Meiotic recombination is initiated by the deliberate introduction of DNA double-strand breaks (DSBs). During meiosis, the ends of these programmed DSBs are processed to generate 3′ single-stranded DNA (ssDNA) overhangs, which serve as primers for DNA repair. The recombinases RAD51 and DMC1 are loaded onto the ssDNA overhangs to form a presynaptic filament, a critical intermediate required for homologous recombination (HR) repair. Several HR factors play important regulatory roles in meiotic recombination. BRCA2 recruits recombinases to DNA break sites and therefore plays a key role in their localization during DSB repair. MEILB2 is a meiosis-specific HR factor that localizes to programmed DSB sites and facilitates the recruitment of BRCA2. SYCP3, a core component of the lateral element of the synaptonemal complex, contributes to chromatin loop stabilization and chromosome axis organization. This dissertation focuses on elucidating the functional roles of MEILB2, SYCP3, and BRCA2 in meiotic HR. In Chapter 2, we examine the function of MEILB2 in regulating recombinase activity. In Chapter 3, we investigate the effect of MEILB2 on accessory proteins involved in recombinase regulation. In Chapter 4, we study SYCP3 and its impact on factors that regulate RAD51. In Chapter 5, we identify a novel DNA-binding region in BRCA2 and demonstrate its role in regulating DMC1 activity. Understanding the functional roles of these proteins in meiotic HR is crucial, as defects in DNA repair pathways are associated with various disorders, including cancer and infertility.

Available for download on Tuesday, August 31, 2027

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