Damage-induced phosphorylation of BRC-1/BRD-1 in meiosis preserves germline integrity.

Abstract

Multiple DNA repair pathways have evolved to safeguard genome integrity and ensure organismal viability in the face of DNA damage. Errors in DNA repair processes in meiosis can lead to aneuploidy and developmental defects, but the processes that protect the germline from DNA damage remain poorly understood. Here we report a DNA damage-induced phosphorylation of the BRC-1/BRD-1 heterodimer that is essential for germline integrity in Caenorhabditis elegans. Failure to phosphorylate BRC-1/BRD-1 in response to DNA damage results in meiotic double-strand breaks (DSBs) accumulation, chromosome breakage, catastrophic diakinesis, and loss of fecundity. We further show that these defects are driven by the activity of C. elegans Bloom and Mus81, which catalyze Holliday junction dissolution and resolution, respectively. Hence, we propose that phosphorylation of BRC-1/BRD-1 in response to ionizing radiation-induced DSBs constitutes a key regulatory step that ensures the proper resolution of recombination intermediates required to preserve germline integrity.