A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis.
A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis.
复制标题
DOI：
10.1083/jcb.201511080
复制
发表时间：
2016-06-20
期刊：
影响因子：
--
通讯作者：
Clarke DJ
中科院分区：
文献类型：
--
作者：
Edgerton H;Johansson M;Keifenheim D;Mukherjee S;Chacón JM;Bachant J;Gardner MK;Clarke DJ
Topo II 的 C 末端结构域 (CTD) 因其催化活性而显得可有可无，但对于有丝分裂期间染色体分离中的 Topo II 功能却至关重要。在这里，埃杰顿等人。解析了 Topo II CTD 在酵母有丝分裂过程中的作用，表明它通过 Haspin-H3 T3-Phos 途径以非催化方式发挥作用，将 Ipl1/Aurora B 招募到有丝分裂内部着丝粒。忠实的染色体分离取决于染色单体分离的精确时间，这是由动粒产生的检查点信号强制执行的。在这里，我们提供的证据表明，DNA 拓扑异构酶 IIα (Topo II) 的 C 末端结构域 (CTD) 在有丝分裂中着丝粒的内部着丝粒提供了一种新功能。我们发现，在中期，酵母 CTD 是张力检查点激酶 Ipl1/Aurora B 募集至内部着丝粒所必需的，但在间期则不需要。 Ipl1 招募需要保守的 CTD SUMO 化位点。这种内着丝粒 CTD 功能与 Topo II 的催化活性不同。遗传和生化证据表明，Topo II 通过 Haspin-组蛋白 H3 苏氨酸 3 磷酸化途径招募 Ipl1。最后，Topo II 和 Sgo1 对于 Ipl1 募集到内部着丝粒同样重要。这表明 H3 T3-Phos/H2A T120-Phos 是一种通用表观遗传特征，定义真核生物内部着丝粒并为 Ipl1/Aurora B 提供结合位点。
The C-terminal domain (CTD) of Topo II is dispensable for its catalytic activity yet essential for Topo II function in chromosome segregation during mitosis. Here, Edgerton et al. resolve the role of the Topo II CTD during mitosis in yeast, showing that it functions noncatalytically via the Haspin-H3 T3-Phos pathway to recruit Ipl1/Aurora B to mitotic inner centromeres. Faithful chromosome segregation depends on the precise timing of chromatid separation, which is enforced by checkpoint signals generated at kinetochores. Here, we provide evidence that the C-terminal domain (CTD) of DNA topoisomerase IIα (Topo II) provides a novel function at inner centromeres of kinetochores in mitosis. We find that the yeast CTD is required for recruitment of the tension checkpoint kinase Ipl1/Aurora B to inner centromeres in metaphase but is not required in interphase. Conserved CTD SUMOylation sites are required for Ipl1 recruitment. This inner-centromere CTD function is distinct from the catalytic activity of Topo II. Genetic and biochemical evidence suggests that Topo II recruits Ipl1 via the Haspin–histone H3 threonine 3 phosphorylation pathway. Finally, Topo II and Sgo1 are equally important for Ipl1 recruitment to inner centromeres. This indicates H3 T3-Phos/H2A T120-Phos is a universal epigenetic signature that defines the eukaryotic inner centromere and provides the binding site for Ipl1/Aurora B.