Garcia-Muse, TatianaGalindo-Diaz, UGarcia-Rubio, MMartin, J SPolanowska, JO'Reilly, NAguilera, ABoulton, Simon J2023-01-252023-01-252019http://hdl.handle.net/10668/13427Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ATR/ATMBRC-1DNA damage responseDNA double-strand breaksinter-sister repairmeiosissynaptonemal complexAnimalsCaenorhabditis elegansCell Cycle CheckpointsDNA Breaks, Double-StrandedDNA DamageDNA-Binding ProteinsMeiosisresearch article30650366open access10.1016/j.celrep.2018.12.0742211-1247PMC6334227http://www.cell.com/article/S2211124718320199/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334227/pdf