Tension sensing by Aurora B kinase is independent of survivin-based centromere localization.

Tension sensing by Aurora B kinase is independent of survivin-based centromere localization.
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DOI:
10.1038/nature12057
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发表时间:
2013-05-02
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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复制基因组的精确分离需要染色体在纺锤体上的双向定位。双定向由Aurora B激酶确保,Aurora B激酶是4亚基染色体乘客复合物(CPC)的成员。CPC定位于内部着丝粒是当前模型的核心,该模型用于确定张力如何确保不在张力下的染色体生物取向-动粒-纺锤体附件保持靠近内部着丝粒,并且通过极光B磷酸化而不稳定,而在张力下的动粒被拉离极光B的影响,稳定它们的微管附件。在这里,我们表明,工程截断的INCENP/Sli 15亚基的芽殖酵母CPC,消除与内部着丝粒,但支持适当的染色体分离在有丝分裂和减数分裂。截短的INCENP/Sli 15抑制内着丝粒靶向蛋白Survivin/Bir 1、Borealin/Nbl 1、Bub 1和Sgo 1的缺失表型。与野生型INCENP/Sli 15不同,截短的INCENP/Sli 15定位于后期前纺锤体微管。通过阻止Cdk 1磷酸化将全长INCENP/Sli 15过早靶向微管也抑制了Survivin/Bir 1缺失的不活性。这些结果表明,激活极光B/Ipl 1的染色质或微管上的集群是足够的染色体双取向。
Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase, a member of the 4-subunit chromosomal passenger complex (CPC). Localization of the CPC to the inner centromere is central to the current model for how tension ensures chromosome biorientation—kinetochore-spindle attachments not under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments. Here we show that an engineered truncation of the INCENP/Sli15 subunit of budding yeast CPC that eliminates association with the inner centromere nevertheless supports proper chromosome segregation during both mitosis and meiosis. Truncated INCENP/Sli15 suppresses the deletion phenotypes of the inner centromere-targeting proteins Survivin/Bir1, Borealin/Nbl1, Bub1 and Sgo1. Unlike wildtype INCENP/Sli15, truncated INCENP/Sli15 localizes to pre-anaphase spindle microtubules. Premature targeting of full-length INCENP/Sli15 to microtubules by preventing Cdk1 phosphorylation also suppresses inviability of Survivin/Bir1 deletion. These results suggest that activation of Aurora B/Ipl1 by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation.
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