School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Cell Cycle. 2021 Oct;20(20):2077-2090. doi: 10.1080/15384101.2021.1970877. Epub 2021 Sep 16.
To ensure genome stability, chromosomes need to undergo proper condensation into two linked sister chromatids from prophase to prometaphase, followed by equal segregation at anaphase. Emerging evidence has shown that persistent DNA entanglements connecting the sister chromatids lead to the formation of ultrafine anaphase bridges (UFBs). If UFBs are not resolved soon after anaphase, they can induce chromosome missegregation. PICH (PLK1-interacting checkpoint helicase) is a DNA translocase that localizes on chromosome arms, centromeres and UFBs. It plays multiple essential roles in mitotic chromosome organization and segregation. PICH also recruits other associated proteins to UFBs, and together they mediate UFB resolution. Here, the proposed mechanism behind PICH's functions in chromosome organization and UFB resolution will be discussed. We summarize the regulation of PICH action at chromosome arms and centromeres, how PICH recognizes UFBs and recruits other UFB-associated factors, and finally how PICH promotes UFB resolution together with other DNA processing enzymes.
为了确保基因组的稳定性,染色体需要在从前期到前中期经历适当的凝聚,形成两个相连的姐妹染色单体,然后在后期进行均等分离。新出现的证据表明,连接姐妹染色单体的持续 DNA 纠结会导致超微后期桥(UFB)的形成。如果 UFB 在后期后不久不能解决,它们会导致染色体错误分离。PICH(PLK1 相互作用的检查点螺旋酶)是一种 DNA 转位酶,位于染色体臂、着丝粒和 UFB 上。它在有丝分裂染色体的组织和分离中发挥多种重要作用。PICH 还招募其他相关蛋白到 UFB 上,它们共同介导 UFB 的解决。在这里,将讨论 PICH 在染色体组织和 UFB 解决中的功能背后的拟议机制。我们总结了 PICH 在染色体臂和着丝粒上的作用的调节、PICH 如何识别 UFB 并招募其他 UFB 相关因子,以及 PICH 如何与其他 DNA 处理酶一起促进 UFB 的解决。