Recruitment and dynamics of DNA repair proteins at sites of complex DNA damage within the Caenorhabditis Elegans germline

Gametes are produced through meiotic division; a tightly regulated process in which the amount of DNA is halved. Gametes are naturally subjected to exogenous agents that induce DNA damage (e.g., UV irradiation). Improper repair of DNA damage can lead to mutations or chromosomal abnormalities that can be passed to the next generation. A particularly deleterious form of DNA damage is a double strand break (DSB), in which both strands of the DNA are broken. Furthermore, DSBs can occur in close proximity to each other (complex DNA damage), making it even harder to repair each DSB faithfully. There are two main pathways by which these breaks can be repaired: non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ is considered an error-prone form of repair while HR is considered error-free. Natural meiotic DSBs are exclusively repaired by HR. However, the mechanisms that ensure HR are not in place at sites of exogenous damage. This thesis examines regulation of DNA repair proteins in the meiotic tissue of a transparent nematode, Caenorhabditis elegans, following induction of complex DNA damage via microirradiation. We show that the recruitment of DNA repair proteins is modulated based on the meiotic stage in which damage is induced, and that DSBs exhibit increased motion and relocalization within the nucleus. We also present evidence for the recruitment of both NHEJ and HR proteins to sites of complex DNA damage. This thesis provides valuable insight into the recruitment of repair proteins to sites of complex DNA damage in a meiotic context.