Characterizing DNA Double Strand Break Repair Pathways in Stem Cell-Derived Neurons

DNA double-stranded breaks (DSBs) are one of the most cytotoxic forms of genomic damage. While proliferating cells rely on both homologous recombination (HR) and non-homologous end joining (NHEJ) to maintain genomic integrity, post-mitotic neurons lack a sister chromatid, biasing repair to NHEJ (Ciccia and Elledge, 2010). However, emerging evidence suggests that canonical DNA repair proteins persist in mature neurons, potentially adopting alternative roles that are critical for neuronal function (Herrup and Yang, 2007). We aim to characterize the dynamics and adaptation of DSB repair pathways during human induced pluripotent stem cell (iPSC)-derived neuronal differentiation. By quantifying HR and NHEJ activity and examining the localization and quantification of key repair proteins (e.g., BRCA1, RAD51, 53BP1), this study will examine how DNA repair mechanisms evolve during neuronal maturation and provide insight into how neurons maintain genomic stability.