He Ying, Tang Xiaoya, Fu Hao, Tang Yihang, Lin Honghui, Deng Xingguang
Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.
Sci Adv. 2025 Feb 7;11(6):eadq4033. doi: 10.1126/sciadv.adq4033. Epub 2025 Feb 5.
Proper chromosome segregation during cell division is essential for genomic integrity and organismal development. This process is monitored by the spindle assembly checkpoint (SAC), which delays anaphase onset until all chromosomes are properly attached to the mitotic spindle. The kinetochore protein KNL1 plays a critical role in recruiting SAC proteins. Here, we reveal that KNL1 regulates SAC silencing through the direct recruitment of type one protein phosphatase (TOPP) to kinetochores. We show that KNL1 interacts with all nine TOPPs via a conserved RVSF motif in its N terminus, and this interaction is required for the proper localization of TOPPs to kinetochores during mitosis. Disrupting KNL1-TOPP interaction leads to persistent SAC activation, resulting in a severe metaphase arrest and defects in plant growth and development. Our findings highlight the evolutionary conservation of KNL1 in coordinating kinetochore-localized phosphatase to ensure timely SAC silencing and faithful chromosome segregation in .
细胞分裂过程中正确的染色体分离对于基因组完整性和生物体发育至关重要。这一过程由纺锤体组装检查点（SAC）监控，该检查点会延迟后期开始，直到所有染色体都正确附着到有丝分裂纺锤体上。动粒蛋白KNL1在招募SAC蛋白方面起着关键作用。在这里，我们揭示KNL1通过将1型蛋白磷酸酶（TOPP）直接招募到动粒来调节SAC沉默。我们表明，KNL1通过其N端保守的RVSF基序与所有九种TOPP相互作用，这种相互作用是有丝分裂期间TOPP正确定位于动粒所必需的。破坏KNL1-TOPP相互作用会导致SAC持续激活，从而导致严重的中期停滞以及植物生长发育缺陷。我们的发现突出了KNL1在协调动粒定位磷酸酶以确保及时的SAC沉默和忠实的染色体分离方面的进化保守性。
