Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea;
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):E9261-E9270. doi: 10.1073/pnas.1705261114. Epub 2017 Oct 16.
Rad52 is well known as a key factor in homologous recombination. Here, we report that Rad52 has functions unrelated to homologous recombination in ; it plays a role in the recruitment of Mps1 to the kinetochores and the maintenance of spindle assembly checkpoint (SAC) activity. Deletion of causes various phenotypes related to the dysregulation of chromosome biorientation. Rad52 directly affects efficient operation of the SAC and accurate chromosome segregation. Remarkably, by using an in vitro kinase assay, we found that Rad52 is a substrate of Ipl1/Aurora and Mps1 in yeast and humans. Ipl1-dependent phosphorylation of Rad52 facilitates the kinetochore accumulation of Mps1, and Mps1-dependent phosphorylation of Rad52 is important for the accurate regulation of the SAC under spindle damage conditions. Taken together, our data provide detailed insights into the regulatory mechanism of chromosome biorientation by mitotic kinases.
Rad52 作为同源重组的关键因子而广为人知。在这里,我们报告 Rad52 在酵母中具有与同源重组无关的功能;它在将 Mps1 招募到着丝粒和维持纺锤体检查点(SAC)活性中发挥作用。删除 导致与染色体双定向调控失调相关的各种表型。Rad52 直接影响 SAC 的有效运作和染色体的准确分离。值得注意的是,通过使用体外激酶测定法,我们发现 Rad52 是酵母和人类中 Ipl1/Aurora 和 Mps1 的底物。Rad52 的 Ipl1 依赖性磷酸化有助于 Mps1 在着丝粒上的积累,而 Rad52 的 Mps1 依赖性磷酸化对于在纺锤体损伤条件下准确调节 SAC 是重要的。总之,我们的数据提供了对有丝分裂激酶调节染色体双定向的详细机制的深入了解。