Impeding DNA Break Repair Enables Oocyte Quality Control

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Chromosome Pairing / genetics
  • DNA Breaks, Double-Stranded
  • DNA Damage / genetics*
  • DNA Repair / genetics*
  • Female
  • Ligases / genetics
  • Male
  • Meiosis / genetics
  • Mice
  • Oocytes / physiology*
  • Quality Control
  • Recombination, Genetic / genetics


  • Cell Cycle Proteins
  • Ligases