期刊
GENES & DEVELOPMENT
卷 22, 期 17, 页码 2400-2413出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.475308
关键词
cohesion; chromosome segregation; Shugoshin-2; mouse; mitosis; meiosis
资金
- J CyLe (SA)
- CSIC [2006 2 01 051]
- Fundacion Mutua Madrilena
- FIS
- FPI
- Ramon y Cajal Research contract
- Junta de Castilla y Leon
- MEC [BFU2005-05668-C03-01/BCM, BFU2006-04406/BMC]
- UAM/Comunidad de Madrid [CCG06-UAM/SAL-0260]
- CAM [P-BIO-0189-2006]
- [SAF-2005-01993]
Shugoshin-2 (SGOL2) is one of the two mammalian orthologs of the Shugoshin/Mei-S322 family of proteins that regulate sister chromatid cohesion by protecting the integrity of the multiprotein cohesin complexes. This protective system is essential for faithful chromosome segregation during mitosis and meiosis, which is the physical basis of Mendelian inheritance. Regardless of its evolutionary conservation from yeast to mammals, little is known about the in vivo relevance and specific role that SGOL2 plays in mammals. Here we show that disruption of the gene encoding mouse SGOL2 does not cause any alteration in sister chromatid cohesion in embryonic cultured fibroblasts and adult somatic tissues. Moreover, mutant mice develop normally and survive to adulthood without any apparent alteration. However, both male and female Sgol2-deficient mice are infertile. We demonstrate that SGOL2 is necessary for protecting centromeric cohesion during mammalian meiosis I. In vivo, the loss of SGOL2 promotes a premature release of the meiosis-specific REC8 cohesin complexes from anaphase I centromeres. This molecular alteration is manifested cytologically by the complete loss of centromere cohesion at metaphase II leading to single chromatids and physiologically with the formation of aneuploid gametes that give rise to infertility.
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