Dear Editor,Chromosome segregation in eukary-otes relies on intricate interactions between spindle microtubules and centromeres(Liu et al,2020).Recently,using cryo-electron microscopy(cryo-EM)alongside functional anal...Dear Editor,Chromosome segregation in eukary-otes relies on intricate interactions between spindle microtubules and centromeres(Liu et al,2020).Recently,using cryo-electron microscopy(cryo-EM)alongside functional analyses,we and other groups unveiled the molecular basis of how human kinetochore constitutive centromere-associated network(CCAN)interacts with duplex DNA and facilitates accurate chromosome segregation(Pesenti et al,2022;Tian et al.,2022;Yatskevich et al,.2022).While these investigations offer a foundational understanding of the physical and chemical interdependency of CCAN constituents,the functional significance of individual contacts within this complex remains to be fully elucidated.展开更多
Dear Editor,During mitosis,the precise separation of chromosomes relies on the accurate connection between kinetochores and microtubules(Liu et al.,2020).Centromere protein C(CENP-C)is a central hub for kinetochore as...Dear Editor,During mitosis,the precise separation of chromosomes relies on the accurate connection between kinetochores and microtubules(Liu et al.,2020).Centromere protein C(CENP-C)is a central hub for kinetochore assembly and its cell-cycle function depends on post-translational modifications.Previous yeast and Caenorhabditis elegans studies suggest that the mitotic kinase polo-like kinase 1(PLK1)binds to the PEST-rich domain of CENP-C(Hinshaw et al.,2023;Taylor et al.,2023).Yeast CENP-C can be co-phosphorylated at 11 sites by DDK and CDC5(yeast PLK1),facilitating the assembly of the inner kinetochore,the constitutive centromere-associated network(CCAN).However,these phosphorylation sites are not conserved in humans(Hinshaw et al.,2023),raising the question of whether PLK1 regulates human inner kinetochore assembly via CENP-C.展开更多
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,92153302,W2411017,32400593,92253301,22137007,and 92053104)the Plansfor Major Provincial Science&Technology Projects of Anhui Province(202303a0702003).F.A.,L.Z.,X.L.,and X.Y.conceived the project and designed the experiments.O.A.D.and X.G.performed the chemical screening.O.A.D.and F.Y.performed the experiments and analyzed the data.O.A.D.,L.Z.,and X.Y.wrote the manuscript.X.L.and X.Y.supervised the project.
文摘Dear Editor,Chromosome segregation in eukary-otes relies on intricate interactions between spindle microtubules and centromeres(Liu et al,2020).Recently,using cryo-electron microscopy(cryo-EM)alongside functional analyses,we and other groups unveiled the molecular basis of how human kinetochore constitutive centromere-associated network(CCAN)interacts with duplex DNA and facilitates accurate chromosome segregation(Pesenti et al,2022;Tian et al.,2022;Yatskevich et al,.2022).While these investigations offer a foundational understanding of the physical and chemical interdependency of CCAN constituents,the functional significance of individual contacts within this complex remains to be fully elucidated.
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,W2411017,2022YFA0806800,and 92153302)the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003)+2 种基金the Ministry of Education(IRT_17R102)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)the Fundamental Research Funds for the Central Universities(KB9100000007,KB9100000006,and KB9100000013).
文摘Dear Editor,During mitosis,the precise separation of chromosomes relies on the accurate connection between kinetochores and microtubules(Liu et al.,2020).Centromere protein C(CENP-C)is a central hub for kinetochore assembly and its cell-cycle function depends on post-translational modifications.Previous yeast and Caenorhabditis elegans studies suggest that the mitotic kinase polo-like kinase 1(PLK1)binds to the PEST-rich domain of CENP-C(Hinshaw et al.,2023;Taylor et al.,2023).Yeast CENP-C can be co-phosphorylated at 11 sites by DDK and CDC5(yeast PLK1),facilitating the assembly of the inner kinetochore,the constitutive centromere-associated network(CCAN).However,these phosphorylation sites are not conserved in humans(Hinshaw et al.,2023),raising the question of whether PLK1 regulates human inner kinetochore assembly via CENP-C.
