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Resources » Paper

Garcia-Muse T et al. (2019) Cell Rep "A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs."

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  • Comments on Garcia-Muse T et al. (2019) Cell Rep "A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs." (0)

  • Overview

    PMID:
    30650366
    DOI:
    10.1016/j.celrep.2018.12.074
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00056153

    Garcia-Muse T, Galindo-Diaz U, Garcia-Rubio M, Martin JS, Polanowska J, O'Reilly N, Aguilera A, & Boulton SJ (2019). A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs. Cell Rep, 26, 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-1<sup>6A</sup>) or dephosphorylate (syp-1<sup>6D</sup>) 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<sup>BRCA1</sup>. 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.

    Authors: Garcia-Muse T, Galindo-Diaz U, Garcia-Rubio M, Martin JS, Polanowska J, O'Reilly N, Aguilera A, Boulton SJ


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