Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates

Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates
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DOI:
10.1016/j.molcel.2005.03.017
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发表时间:
2005-04-15
期刊:
影响因子:
16
通讯作者:
Kirschner, MW
Kirschner, MW
中科院分区:
生物学1区
文献类型:
--
作者:
Rankin, S;Ayad, NG;Kirschner, MW

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我们已经确定了一个调节姐妹染色单体凝聚力的细胞周期控制蛋白的屏幕。这种35 kDa的蛋白质通过后期促进复合物(APC)依赖的泛素化在G1降解。该蛋白质在间期细胞的核中,在有丝分裂中从染色质中分散,并与粘着蛋白复合物相互作用。在非洲爪蟾胚胎中,蛋白质的过度表达导致在有丝分裂中不能分辨和分离姐妹染色单体,以及与中期染色体相关的粘着素水平的增加。在培养的细胞中,蛋白质的耗尽导致有丝分裂停滞和姐妹染色单体凝聚的完全失败。因此,这种蛋白质是姐妹染色单体凝聚力的一种重要的细胞周期依赖性介质。基于序列分析,该蛋白在脊椎动物之外没有明显的直系同源物。我们推测,蛋白质,我们命名为sororin,调节的能力,cohesin复合体介导姐妹染色单体凝聚力,也许是通过改变的性质的相互作用的cohesin与染色体。
We have identified a regulator of sister chromatid cohesion in a screen for cell cycle-controlled proteins. This 35 kDa protein is degraded through anaphase-promoting complex (APC)-dependent ubiquitination in G1. The protein is nuclear in interphase cells, dispersed from the chromatin in mitosis, and interacts with the cohesin complex. In Xenopus embryos, overexpression of the protein causes failure to resolve and segregate sister chromatids in mitosis and an increase in the level of cohesin associated with metaphase chromosomes. In cultured cells, depletion of the protein causes mitotic arrest and complete failure of sister chromatid cohesion. This protein is thus an essential, cell cycle-dependent mediator of sister chromatid cohesion. Based on sequence analysis, this protein has no apparent orthologs outside of the vertebrates. We speculate that the protein, which we have named sororin, regulates the ability of the cohesin complex to mediate sister chromatid cohesion, perhaps by altering the nature of the interaction of cohesin with the chromosomes.