MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China School of Life Sciences, Hefei 230027, China.
Keck Center for Cellular Dynamics and Organoids Plasticity, Atlanta, GA 30310, USA.
J Mol Cell Biol. 2024 Jul 29;16(2). doi: 10.1093/jmcb/mjae001.
Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.
在有丝分裂中,准确的染色体分离依赖于将着丝粒染色质连接到纺锤体微管的动粒。在染色体分离过程中,着丝粒通过动粒组成性着丝粒相关网络(CCAN)被单个微管捕获。CCAN 包含 16 个亚基,包括 CENP-W 和 CENP-T。然而,CCAN 组装的分子识别和有丝分裂调节仍然难以捉摸。在这里,我们揭示了 CENP-W 与 CENP-T 的组蛋白折叠结构域和未鉴定的 N 端区域结合。极光激酶 B 将 CENP-W 的苏氨酸 60 磷酸化,增强了 CENP-W 与 CENP-T 之间的相互作用,以确保中期染色体的正确排列和有丝分裂中染色体的准确分离。这些发现描绘了一个保守的信号级联,将蛋白磷酸化与 CCAN 的完整性整合在一起,以维持基因组的稳定性。