RT Journal Article
T1 A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs.
A1 Garcia-Muse, Tatiana
A1 Galindo-Diaz, U
A1 Garcia-Rubio, M
A1 Martin, J S
A1 Polanowska, J
A1 O'Reilly, N
A1 Aguilera, A
A1 Boulton, Simon J
K1 ATR/ATM
K1 BRC-1
K1 DNA damage response
K1 DNA double-strand breaks
K1 inter-sister repair
K1 meiosis
K1 synaptonemal complex
AB 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.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/13427
UL http://hdl.handle.net/10668/13427
LA en
DS RISalud
RD Apr 18, 2025