Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis
Year: 2023
Type: article
Abstract: In mitosis, accurate chromosome segregation depends on the kinetochore, a supermolecular machinery that couples dynamic spindle microtubules to centromeric chromatin. However, the structure-activity relationship of the constitutive centromere-associated network (CCAN) during mitosis remains uncharacterized. Building on our recent cryo-electron microscopic analyses of human CCAN structure, we investigated how dynamic phosphorylation of human CENP-N regulates accurate chromosome segregation. Our mass spectrometric analyses revealed mitotic phosphorylation of CENP-N by CDK1, which modulates the CENP-L-CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation is shown to prevent proper chromosome alignment and activate the spindle assembly checkpoint. These analyses provide mechanistic insight into a previously undefined link between the centromere-kinetochore network and accurate chromosome segregation.
DOI: 10.1093/jmcb/mjad041
Authors: Ran Liu, Zhen Dou, Tian Tian, Xinjiao Gao, Lili Chen, Xiao Yuan, Chunyue Wang, Jiahe Hao, Ping Gui, McKay Mullen, Felix Aikhionbare, Liwen Niu, Guoqiang Bi, Peng Zou, Xuan Zhang, Chuanhai Fu, Xuebiao Yao, Jianye Zang, Xing Liu
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,600
Funders: National Natural Science Foundation of China, Chinese Academy of Sciences, Ministry of Science and Technology of the People's Republic of China, Ministry of Education and Science of the Republic of Kazakhstan, University of Science and Technology of China, Natural Science Foundation of Anhui Province, Fundamental Research Funds for the Central Universities
Awards: G1250500999, G1291478364, G1391197667, G1451042286, G1639942686, G1639991185, G1652062804, G1661449836, G1941492344, G207798127, G2363142608, G2620996655, G2871916073, G3101856360, G3616747661, G3878596989, G4011972325, G4022343198, G4026607601, G4056952099, G4194134909, G4228310001, G4689913977, G4748013812, G4787304968, G5183096191, G5953861108, 微管正端跟踪蛋白EB1动态巴豆酰化调控细胞有丝分裂的机制解析, G6126115511, G6198463019, G6201305180, G6210758682, G6347094549, G655193879, G6956408019, G7227280788, G7305002525, G7393269614, G7626018381, G8121644851, G8137223251, G829647422, G8620937303, G868479599, G8710964044, G8748993011, G8751836537, G901699769
OpenAlex ID: W4382181885