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Mol Cell. 2018 Oct 18;72(2):211-221.e3. doi: 10.1016/j.molcel.2018.08.031. Epub 2018 Sep 27.

Impeding DNA Break Repair Enables Oocyte Quality Control.

Author information

1
Howard Hughes Medical Institute, University of California, Davis, Davis, CA, USA; Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, CA, USA. Electronic address: hqiao@illinois.edu.
2
Howard Hughes Medical Institute, University of California, Davis, Davis, CA, USA; Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, CA, USA.
3
Howard Hughes Medical Institute, University of California, Davis, Davis, CA, USA; Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, CA, USA; Department of Molecular & Cellular Biology, University of California, Davis, Davis, CA, USA; Department of Cell Biology & Human Anatomy, University of California, Davis, Davis, CA, USA. Electronic address: nhunter@ucdavis.edu.

Abstract

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocyte elimination in meiotic mutants require RNF212. RNF212 sensitizes oocytes to DSB-induced apoptosis within a narrow window as chromosomes desynapse and cells transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality-control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

KEYWORDS:

HORMAD; RNF212; SUMO; apoptosis; attrition; double strand break; follicle; homologous recombination; meiosis; oocyte

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