Polisetty Satya Dev, Bhat Krishna, Das Kuladeep, Clark Ivan, Hardwick Kevin G, Sanyal Kaustuv
Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India.
Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
PLoS Genet. 2025 Jan 13;21(1):e1011552. doi: 10.1371/journal.pgen.1011552. eCollection 2025 Jan.
During chromosome segregation, the spindle assembly checkpoint (SAC) detects errors in kinetochore-microtubule attachments. Timely activation and maintenance of the SAC until defects are corrected is essential for genome stability. Here, we show that shugoshin (Sgo1), a conserved tension-sensing protein, ensures the maintenance of SAC signals in response to unattached kinetochores during mitosis in a basidiomycete budding yeast Cryptococcus neoformans. Sgo1 maintains optimum levels of Aurora B kinase Ipl1 and protein phosphatase 1 (PP1) at kinetochores. The absence of Sgo1 results in the loss of Aurora BIpl1 with a concomitant increase in PP1 levels at kinetochores. This leads to a premature reduction in the kinetochore-bound Bub1 levels and early termination of the SAC signals. Intriguingly, the kinase function of Bub1 is dispensable for shugoshin's subcellular localization. Sgo1 is predominantly localized to spindle pole bodies (SPBs) and along the mitotic spindle with a minor pool at kinetochores. In the absence of proper kinetochore-microtubule attachments, Sgo1 reinforces the Aurora B kinaseIpl1-PP1 phosphatase balance, which is critical for prolonged maintenance of the SAC response.
在染色体分离过程中，纺锤体组装检查点（SAC）检测动粒-微管附着中的错误。在缺陷得到纠正之前及时激活并维持SAC对于基因组稳定性至关重要。在此，我们表明，守护蛋白（Sgo1）是一种保守的张力感应蛋白，在担子菌酵母新型隐球菌有丝分裂期间，它能确保在动粒未附着时维持SAC信号。Sgo1维持动粒处极光激酶B Ipl1和蛋白磷酸酶1（PP1）的最佳水平。Sgo1缺失导致动粒处极光激酶B Ipl1丧失，同时PP1水平升高。这导致动粒结合的Bub1水平过早降低以及SAC信号提前终止。有趣的是，Bub1的激酶功能对于守护蛋白的亚细胞定位并非必需。Sgo1主要定位于纺锤极体（SPB）并沿着有丝分裂纺锤体分布，在动粒处有少量分布。在动粒-微管附着不正确的情况下，Sgo1加强极光激酶B Ipl1-PP1磷酸酶平衡，这对于长期维持SAC反应至关重要。
