RRC ID 88007
Author Fernández-Fernández N, Chacón M, Camino LP, Garcia-Muse T.
Title Damage-induced phosphorylation of BRC-1/BRD-1 in meiosis preserves germline integrity.
Journal Nucleic Acids Res
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.
Volume 53(18)
Published 2025-9-23
DOI 10.1093/nar/gkaf945
PII 8262768
PMID 40990247
PMC PMC12458078
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / radiation effects Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism DNA Breaks, Double-Stranded DNA Damage DNA Repair DNA-Binding Proteins / metabolism Germ Cells* / metabolism Germ Cells* / radiation effects Meiosis* / genetics Meiosis* / radiation effects Phosphorylation
Resource
C.elegans tm1937 tm2026 tm1145