%0 Journal Article
%A Garcia-Muse, Tatiana
%A Galindo-Diaz, U
%A Garcia-Rubio, M
%A Martin, J S
%A Polanowska, J
%A O'Reilly, N
%A Aguilera, A
%A Boulton, Simon J
%T A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs.
%D 2019
%U http://hdl.handle.net/10668/13427
%X 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.
%K ATR/ATM
%K BRC-1
%K DNA damage response
%K DNA double-strand breaks
%K inter-sister repair
%K meiosis
%K synaptonemal complex
%~