Deparment of Pharmacology, Howard Hughes Medical Institute, Dallas, TX, USA.
EMBO J. 2011 Jul 8;30(16):3309-21. doi: 10.1038/emboj.2011.226.
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.
着丝粒为动粒的形成提供核小体，对于有丝分裂过程中的染色体分离至关重要。SNF2 家族解旋酶 PICH（Plk1 相互作用的检查点解旋酶）和 BLM（布卢姆综合征蛋白）解旋酶修饰连接分离姐妹着丝粒的超微细线，这些细线在后期出现。然而，目前尚不清楚 PICH 和 BLM 在这些细线上的功能。在这里，我们发现 PICH 与 BLM 结合，并使 BLM 定位于后期着丝粒细线上。PICH 或 BLM-RNAi 细胞在后期无法解决这些线程。这些断裂的细线程在子细胞中形成含有着丝粒染色质的微核。在 PICH 和 BLM-RNAi 细胞中，后期的线程含有组蛋白和着丝粒标记物。重组纯化的 PICH 在体外具有核小体重塑活性。我们提出 PICH 和 BLM 解开着丝粒染色质，并使后期 DNA 线程主要不含核小体，从而使这些线程能够在快速分离的着丝粒之间跨越长距离而不会断裂，并为它们的解决提供时空窗口。
