Format

Send to

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

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

Author information

1
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Av. Américo Vespucio 24, 41092 Seville, Spain; Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK. Electronic address: tatiana.muse@cabimer.es.
2
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Av. Américo Vespucio 24, 41092 Seville, Spain.
3
Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK.
4
DSB Repair Metabolism Laboratory, The Francis Crick Institute, Midland Road, London, UK.
5
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Av. Américo Vespucio 24, 41092 Seville, Spain. Electronic address: aguilo@us.es.
6
Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK; DSB Repair Metabolism Laboratory, The Francis Crick Institute, Midland Road, London, UK. Electronic address: simon.boulton@crick.ac.uk.

Abstract

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

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center