PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution.

PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution.
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PICH和BLM限制了组蛋白与自源的centromeric DNA螺纹并促进其分辨率。

DOI:
10.1038/emboj.2011.226
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发表时间:
2011-07-08
期刊:
影响因子:
11.4
通讯作者:
Yu, Hongtao
Yu, Hongtao
中科院分区:
生物学1区
文献类型:
--
作者:
Ke, Yuwen;Huh, Jae-Wan;Warrington, Ross;Li, Bing;Wu, Nan;Leng, Mei;Zhang, Junmei;Ball, Haydn L.;Li, Bing;Yu, Hongtao

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着丝粒是着丝粒形成的核心,在有丝分裂中对染色体分离至关重要。SNF 2家族解旋酶PICH(Plk 1相互作用检查点解旋酶)和BLM(布卢姆综合征蛋白)解旋酶装饰超细组蛋白阴性DNA丝,在后期连接分离的姐妹着丝粒。然而,PICH和BLM在这些线程中的功能还不清楚。在这里,我们表明,PICH结合BLM,使BLM本地化后期着丝粒线程。PICH-或BLM-RNAi细胞在后期不能解决这些线程。断裂的细丝在子细胞中形成含着丝粒染色质的微核。PICH和BLM-RNAi细胞中的后期丝含有组蛋白和着丝粒标记。重组纯化的PICH在体外具有核小体重塑活性。我们建议,PICH和BLM解开着丝粒染色质,并保持后期DNA线程大多没有核小体,从而使这些线程跨越长距离之间的快速分离着丝粒没有破损,并提供了一个时空窗口,其分辨率。
Centromeres nucleate the formation of kinetochores and are vital for chromosome segregation during mitosis. The SNF2 family helicase PICH (Plk1-interacting checkpoint helicase) and the BLM (the Bloom's syndrome protein) helicase decorate ultrafine histone-negative DNA threads that link the segregating sister centromeres during anaphase. The functions of PICH and BLM at these threads are not understood, however. Here, we show that PICH binds to BLM and enables BLM localization to anaphase centromeric threads. PICH- or BLM-RNAi cells fail to resolve these threads in anaphase. The fragmented threads form centromeric-chromatin-containing micronuclei in daughter cells. Anaphase threads in PICH- and BLM-RNAi cells contain histones and centromere markers. Recombinant purified PICH has nucleosome remodelling activities in vitro. We propose that PICH and BLM unravel centromeric chromatin and keep anaphase DNA threads mostly free of nucleosomes, thus allowing these threads to span long distances between rapidly segregating centromeres without breakage and providing a spatiotemporal window for their resolution.
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