A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

Accurate 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. [Display omitted] •Meiotic DNA damage triggers phosphorylation of the synaptonemal complex (SC)•ATM-ATR kinases phosphorylate the SC in response to excessive meiotic DSBs•SC phosphorylation channels DNA repair to the sister chromatid Garcia-Muse et al. show that the checkpoint kinases ATM and ATR respond to excessive or unrepaired meiotic DSBs by phosphorylating the core synaptonemal complex, which channels repair via the sister chromatid. These findings reveal a mechanism that switches repair partner bias to protect meiotic cells from unscheduled DNA breaks.