Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan; Graduate Program in Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
Curr Biol. 2017 Apr 3;27(7):1005-1012. doi: 10.1016/j.cub.2017.02.066. Epub 2017 Mar 23.
Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3-5]. Hrk1 localization to centromeres depends largely on the cohesin subunit Pds5 in fission yeast [5]; however, it is unknown how Pds5 regulates Hrk1 localization. Here we identify a conserved Hrk1-interacting motif (HIM) in Pds5 and a Pds5-interacting motif (PIM) in Hrk1 in fission yeast. Mutations in either motif result in the displacement of Hrk1 from centromeres. We also show that the mechanism of Pds5-dependent Hrk1 recruitment is conserved in human cells. Notably, the PIM in Haspin/Hrk1 is reminiscent of the YSR motif found in the mammalian cohesin destabilizer Wapl and stabilizer Sororin, both of which bind PDS5 [6-12]. Similarly, and through the same motifs, fission yeast Pds5 binds to Wpl1/Wapl and acetyltransferase Eso1/Eco1, in addition to Hrk1. Thus, we have identified a protein-protein interaction module in Pds5 that serves as a chromatin platform for regulating sister-chromatid cohesion and chromosome bi-orientation.
姐妹染色单体黏合是由 S 期的黏合复合物建立的，并一直持续到中期，此时姐妹染色单体被来自相对两极的微管捕获[1]。含 Aurora-B 的染色体乘客复合物（CPC）通过纠正错误的微管附着，在实现染色体双定向方面发挥着至关重要的作用[2]。CPC 的着丝粒定位在很大程度上依赖于组蛋白 H3-T3 磷酸化（H3-pT3），这是由有丝分裂组蛋白激酶 Haspin/Hrk1 介导的[3-5]。裂殖酵母中，Hrk1 向着丝粒的定位在很大程度上依赖于黏合复合物亚基 Pds5[5]；然而，Pds5 如何调节 Hrk1 的定位尚不清楚。在这里，我们在裂殖酵母中鉴定了 Pds5 中的一个保守的 Hrk1 相互作用基序（HIM）和 Hrk1 中的一个 Pds5 相互作用基序（PIM）。这两个基序中的任何一个突变都会导致 Hrk1 从着丝粒上移位。我们还表明，Pds5 依赖的 Hrk1 募集机制在人类细胞中是保守的。值得注意的是，Haspin/Hrk1 中的 PIM 类似于哺乳动物黏合体解聚剂 Wapl 和稳定蛋白 Sororin 中的 YSR 基序，这两种蛋白都与 PDS5 结合[6-12]。同样，通过相同的基序，裂殖酵母 Pds5 还与 Wpl1/Wapl 和乙酰转移酶 Eso1/Eco1 结合，此外还与 Hrk1 结合。因此，我们已经确定了 Pds5 中的一个蛋白质-蛋白质相互作用模块，它作为一个染色质平台，调节姐妹染色单体黏合和染色体双定向。
