Journal
CELL REPORTS
Volume 26, Issue 3, Pages 775-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.12.074
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Funding
- Francis Crick Institute - Cancer Research UK [FC0010048]
- UK Medical Research Council [FC0010048]
- Wellcome Trust [FC0010048]
- European Research Council (ERC)
- Wellcome Trust
- Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P]
- European Research Council(ERC) [ERC2014 AdG669898 TARLOOP]
- European Union (FEDER)
- CSICJAE-Doc
- Junta de Andalucia Excellence Program [CVI-4567]
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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 phos-phorylates 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-1(6A)) or dephosphorylate (syp-1(6D)) 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-1 BRCA1. 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.
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