Merck

Impeding DNA Break Repair Enables Oocyte Quality Control.

Molecular cell (2018-10-03)
Huanyu Qiao, H B D Prasada Rao, Yan Yun, Sumit Sandhu, Jared H Fong, Manali Sapre, Michael Nguyen, Addy Tham, Benjamin W Van, Tiffany Y H Chng, Amy Lee, Neil Hunter
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tyrode′s Solution, Acidic, liquid, sterile-filtered, suitable for mouse embryo cell culture
Sigma-Aldrich
M2 medium, With HEPES, without penicillin and streptomycin, liquid, sterile-filtered, suitable for mouse embryo cell culture
Sigma-Aldrich
Anti-phospho-Histone H2A.X (Ser139) Antibody, clone JBW301, clone JBW301, Upstate®, from mouse