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

Cell Rep. 2019 Jan 15;26(3):775-787.e5. doi: 10.1016/j.celrep.2018.12.074.


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.

Keywords: ATR/ATM; BRC-1; DNA damage response; DNA double-strand breaks; inter-sister repair; meiosis; synaptonemal complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Cell Cycle Checkpoints / genetics*
  • DNA Breaks, Double-Stranded*
  • DNA Damage / genetics*
  • DNA-Binding Proteins / metabolism*
  • Meiosis


  • DNA-Binding Proteins