Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells

Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells
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DOI:
10.1038/ncb1667
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发表时间:
2008-01-01
影响因子:
21.3
通讯作者:
Watanabe, Yoshinori
Watanabe, Yoshinori
中科院分区:
生物学1区
文献类型:
--
作者:
Lee, Jibak;Kitajima, Tomoya S.;Watanabe, Yoshinori

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生殖细胞中的减数染色体分离,即姐妹染色单体被拉到同一极,伴随着丝粒粘附素的保护,使其免受分离酶的切割。在这里,我们证明了哺乳动物Shugoshin Sgo2在生殖细胞中表达,并单独负责PP2A的着丝粒定位和卵母细胞中粘附素Rec8的保护,证明了从酵母到哺乳动物的保守机制。然而,Sgo2的这种作用与它的有丝分裂作用相反,它只保护着丝粒粘附素不受前期解离,而不能保护着丝粒粘附素免受后期切割。我们证明,在体细胞中,舒戈申蛋白和凝集素在前期或中期共存,但当着丝粒在中期相反拉动时,它们的定位变得分开。值得注意的是,如果在中期-后期转变时人为地消除着丝粒的张力,着丝粒上的粘附素可以被保护,即使在体细胞中也是如此,就像在生殖细胞中一样。这些结果表明,在有丝分裂和减数分裂过程中,Shugoshin对着丝粒的保护具有统一的观点。
Reductional chromosome segregation in germ cells, where sister chromatids are pulled to the same pole, accompanies the protection of cohesin at centromeres from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed in germ cells and is solely responsible for the centromeric localization of PP2A and the protection of cohesin Rec8 in oocytes, proving conservation of the mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its mitotic role in protecting centromeric cohesin only from prophase dissociation, but never from anaphase cleavage. We demonstrate that, in somatic cells, shugoshin colocalizes with cohesin in prophase or prometaphase, but their localizations become separate when centromeres are pulled oppositely at metaphase. Remarkably, if tension is artificially removed from the centromeres at the metaphase-anaphase transition, cohesin at the centromeres can be protected from separase cleavage even in somatic cells, as in germ cells. These results argue for a unified view of centromeric protection by shugoshin in mitosis and meiosis.