Reversal of Female Infertility by Chk2 Ablation Reveals the Oocyte DNA Damage Checkpoint Pathway

作者: E. Bolcun-Filas , V. D. Rinaldi , M. E. White , J. C. Schimenti

DOI: 10.1126/SCIENCE.1247671

关键词:

摘要: Genetic errors in meiosis can lead to birth defects and spontaneous abortions. Checkpoint mechanisms of hitherto unknown nature eliminate oocytes with unrepaired DNA damage, causing recombination-defective mutant mice be sterile. Here, we report that checkpoint kinase 2 (Chk2 or Chek2), is essential for culling mouse bearing meiotic induced double-strand breaks (DSBs). Female infertility caused by a recombination mutation irradiation was reversed Chk2. Both meiotically programmed DSBs trigger CHK2-dependent activation TRP53 (p53) TRP63 (p63), effecting oocyte elimination. These data establish CHK2 as damage surveillance female indicate the DSB response primarily involves pathway hierarchy which ataxia telangiectasia Rad3-related (ATR) signals CHK2, then activates p53 p63.

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