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
{"title":"CDK1 对 CENP-N 的动态磷酸化引导着有丝分裂过程中染色体的准确分离。","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","doi":"10.1093/jmcb/mjad041","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799313/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.\",\"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\",\"doi\":\"10.1093/jmcb/mjad041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":16433,\"journal\":{\"name\":\"Journal of Molecular Cell Biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2023-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799313/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Cell Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/jmcb/mjad041\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/jmcb/mjad041","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.
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.
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The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome.
JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.
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