Trautmann Susanne, Rajagopalan Srividya, McCollum Dannel
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
Dev Cell. 2004 Nov;7(5):755-62. doi: 10.1016/j.devcel.2004.10.006.
The S. pombe Cdc14-related phosphatase Clp1p/Flp1p regulates G2/M transition by antagonizing CDK activity and is essential for coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint. At the G2/M transition, Clp1p/Flp1p is released from the nucleolus and SPB and distributes throughout the nucleus to the spindle and the contractile ring. This early relocalization is analogous to vertebrate Cdc14 homologs and stands in contrast to S. cerevisiae Cdc14p, which is not released from the nucleolus until metaphase/anaphase transition. Here, we report that Clp1p/Flp1p localizes to kinetochores in prometaphase and functions in chromosome segregation, since deletion of clp1/flp1 causes cosegregation of sister chromatids, when sister kinetochores are prone to mono-orientation. Genetic, cytological, and biochemical experiments suggest that Clp1p/Flp1p functions together with Aurora kinase at kinetochores. Together, these results suggest that Clp1p/Flp1p has a role in repairing mono-orientation of sister kinetochores.
粟酒裂殖酵母中与Cdc14相关的磷酸酶Clp1p/Flp1p通过拮抗CDK活性来调节G2/M期转换，并且对于通过胞质分裂检查点协调核分裂周期与胞质分裂至关重要。在G2/M期转换时，Clp1p/Flp1p从核仁与纺锤体极体释放，并在整个细胞核中分布到纺锤体和收缩环。这种早期的重新定位类似于脊椎动物的Cdc14同源物，与酿酒酵母的Cdc14p形成对比，后者直到中期/后期转换时才从核仁中释放。在此，我们报道Clp1p/Flp1p在前中期定位于动粒并在染色体分离中发挥作用，因为当姐妹动粒易于单极定向时，clp1/flp1的缺失会导致姐妹染色单体的共分离。遗传学、细胞学和生物化学实验表明，Clp1p/Flp1p在动粒处与极光激酶共同发挥作用。这些结果共同表明，Clp1p/Flp1p在修复姐妹动粒的单极定向中发挥作用。
