Baumann Christoph, Körner Roman, Hofmann Kay, Nigg Erich A
Department of Cell Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
Cell. 2007 Jan 12;128(1):101-14. doi: 10.1016/j.cell.2006.11.041.
We identify PICH (Plk1-interacting checkpoint "helicase"), a member of the SNF2 ATPase family, as an interaction partner and substrate of Plk1. Following phosphorylation of PICH on the Cdk1 site T1063, Plk1 is recruited to PICH and controls its localization. Starting in prometaphase, PICH accumulates at kinetochores and inner centromeres. Moreover, it decorates threads that form during metaphase before increasing in length and progressively diminishing during anaphase. PICH-positive threads connect sister kinetochores and are dependent on tension, sensitive to DNase, and exacerbated in response to premature loss of cohesins or inhibition of topoisomerase II, suggesting that they represent stretched centromeric chromatin. Depletion of PICH causes the selective loss of Mad2 from kinetochores and completely abrogates the spindle checkpoint, resulting in massive chromosome missegregation. These data identify PICH as a novel essential component of checkpoint signaling. We propose that PICH binds to catenated centromere-related DNA to monitor tension developing between sister kinetochores.
我们鉴定出PICH（与Plk1相互作用的检查点“解旋酶”），它是SNF2 ATP酶家族的成员，是Plk1的相互作用伙伴和底物。在PICH的Cdk1位点T1063发生磷酸化后，Plk1被招募到PICH并控制其定位。从前中期开始，PICH在动粒和内着丝粒处积累。此外，它修饰在中期形成的细丝，这些细丝在后期长度增加并逐渐减少。PICH阳性细丝连接姐妹动粒，依赖于张力，对DNA酶敏感，并且在黏连蛋白过早丢失或拓扑异构酶II受到抑制时加剧，这表明它们代表伸展的着丝粒染色质。PICH的缺失导致动粒上Mad2的选择性丢失，并完全消除纺锤体检查点，导致大量染色体错分离。这些数据确定PICH是检查点信号传导的一种新的必需成分。我们提出，PICH与连环的着丝粒相关DNA结合，以监测姐妹动粒之间产生的张力。
