文档介绍：Separase Phosphosite Mutation Leads to Genome
Instability and Primordial Germ Cell Depletion during
Oogenesis
. .
Juan Xu1 , Meizhi Wang2 , Xinxing Gao1, Bian Hu1, Yinan Du1, Jiankui Zhou1, Xuemei Tian3*, Xingxu
Huang1*
1 Model Animal Research Center, Nanjing University, Nanjing, China, 2 Department of Anatomy, Histology and Embryology, Southern Medical University, Guangzhou,
China, 3 School of Life Science, South China Normal University, Guangzhou, China
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 pletely depleted, a population of
PGCs from mutant females survived Separase deregulation. The surviving pleted 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.
Citation: Xu J, Wang M, Gao X, Hu B, Du Y, et al. (2011) Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during
Oogenesis. PLoS ONE 6(4): e18763. doi:.0018763
Editor: Laszlo Orban, Temasek Life Sciences Laboratory