2019-01-242019-01-242019García Muse, T., Galindo Díaz, U., García Rubio, M.L., Martin, J.S., Polanowska, J., O'Reilly, N.,...,Boulton, S.J. (2019). A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs. Cell Reports, 26 (3), 775-787.e5.2211-1247https://hdl.handle.net/11441/82040Accurate 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.application/pdfengAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/ATR/ATMBRC-1DNA damage responseDNA double-strand breaksInter-sister repairMeiosisSynaptonemal complexinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1016/j.celrep.2018.12.074