MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine (IHM), University of Science and Technology of China School of Life Sciences, Hefei 230026, China.
Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, Hefei National Center for Cross-disciplinary Sciences, Hefei 230027, China.
J Mol Cell Biol. 2024 Apr 4;15(10). doi: 10.1093/jmcb/mjad061.
Shugoshin-1 (Sgo1) is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis. It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120. However, it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1 during mitosis. Here, we show that CENP-A interacts with Sgo1 and determines the localization of Sgo1 to the centromere during mitosis. Further biochemical characterization revealed that lysine and arginine residues in the C-terminal domain of Sgo1 are critical for binding CENP-A. Interestingly, the replacement of these basic amino acids with acidic amino acids perturbed the localization of Sgo1 and Aurora B to the centromere, resulting in aberrant chromosome segregation and premature chromatid separation. Taken together, these findings reveal a previously unrecognized but direct link between Sgo1 and CENP-A in centromere plasticity control and illustrate how the Sgo1-CENP-A interaction guides accurate cell division.
着丝粒蛋白 Sgo1（Sgo1）对于在有丝分裂期间维持姐妹着丝粒的黏合以及确保染色体的正确分离是必需的。已有报道表明 Sgo1 在着丝粒的定位依赖于 Bub1 介导的组蛋白 H2A 在 T120 的磷酸化。然而，其他着丝粒蛋白是否在调节 Sgo1 在有丝分裂期间的定位和功能方面发挥作用仍不确定。在这里，我们发现 CENP-A 与 Sgo1 相互作用，并决定 Sgo1 在有丝分裂期间定位于着丝粒。进一步的生化特性分析表明，Sgo1 的 C 末端结构域中的赖氨酸和精氨酸残基对于结合 CENP-A 是至关重要的。有趣的是，用酸性氨基酸替换这些碱性氨基酸会扰乱 Sgo1 和 Aurora B 向着丝粒的定位，导致染色体分离异常和染色单体过早分离。总之，这些发现揭示了 Sgo1 和 CENP-A 在着丝粒可塑性控制中的一个以前未被认识但直接的联系，并说明了 Sgo1-CENP-A 相互作用如何指导细胞的精确分裂。
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