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Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during Oogenesis

Author

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  • Juan Xu
  • Meizhi Wang
  • Xinxing Gao
  • Bian Hu
  • Yinan Du
  • Jiankui Zhou
  • Xuemei Tian
  • Xingxu Huang

Abstract

To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs) during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis.

Suggested Citation

  • Juan Xu & Meizhi Wang & Xinxing Gao & Bian Hu & Yinan Du & Jiankui Zhou & Xuemei Tian & Xingxu Huang, 2011. "Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during Oogenesis," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-10, April.
  • Handle: RePEc:plo:pone00:0018763
    DOI: 10.1371/journal.pone.0018763
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