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Article: Quantitative differences between cyclin-dependent kinases underlie the unique functions of CDK1 in human cells

TitleQuantitative differences between cyclin-dependent kinases underlie the unique functions of CDK1 in human cells
Authors
Keywordscyclin-dependent kinases
cyclin
genome instability
mitosis
Issue Date2021
Citation
Cell Reports, 2021, v. 37, n. 2, article no. 109808 How to Cite?
AbstractOne of the most intriguing features of cell-cycle control is that, although there are multiple cyclin-dependent kinases (CDKs) in higher eukaryotes, a single CDK is responsible for both G1-S and G2-M in yeasts. By leveraging a rapid conditional silencing system in human cell lines, we confirm that CDK1 assumes the role of G1-S CDK in the absence of CDK2. Unexpectedly, CDK1 deficiency does not prevent mitotic entry. Nonetheless, inadequate phosphorylation of mitotic substrates by noncanonical cyclin B-CDK2 complexes does not allow progression beyond metaphase and underscores deleterious late mitotic events, including the uncoupling of anaphase A and B and cytokinesis. Elevation of CDK2 to a level similar to CDK1 overcomes the mitotic defects caused by CDK1 deficiency, indicating that the relatively low concentration of CDK2 accounts for the defective anaphase. Collectively, these results reveal that the difference between G2-M and G1-S CDKs in human cells is essentially quantitative.
Persistent Identifierhttp://hdl.handle.net/10722/307321
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLau, Ho Wai-
dc.contributor.authorMa, Hoi Tang-
dc.contributor.authorYeung, Tsz Kwan-
dc.contributor.authorTam, Man Yee-
dc.contributor.authorZheng, Danyi-
dc.contributor.authorChu, Siu Ki-
dc.contributor.authorPoon, Randy Yat Choi-
dc.date.accessioned2021-11-03T06:22:22Z-
dc.date.available2021-11-03T06:22:22Z-
dc.date.issued2021-
dc.identifier.citationCell Reports, 2021, v. 37, n. 2, article no. 109808-
dc.identifier.urihttp://hdl.handle.net/10722/307321-
dc.description.abstractOne of the most intriguing features of cell-cycle control is that, although there are multiple cyclin-dependent kinases (CDKs) in higher eukaryotes, a single CDK is responsible for both G1-S and G2-M in yeasts. By leveraging a rapid conditional silencing system in human cell lines, we confirm that CDK1 assumes the role of G1-S CDK in the absence of CDK2. Unexpectedly, CDK1 deficiency does not prevent mitotic entry. Nonetheless, inadequate phosphorylation of mitotic substrates by noncanonical cyclin B-CDK2 complexes does not allow progression beyond metaphase and underscores deleterious late mitotic events, including the uncoupling of anaphase A and B and cytokinesis. Elevation of CDK2 to a level similar to CDK1 overcomes the mitotic defects caused by CDK1 deficiency, indicating that the relatively low concentration of CDK2 accounts for the defective anaphase. Collectively, these results reveal that the difference between G2-M and G1-S CDKs in human cells is essentially quantitative.-
dc.languageeng-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcyclin-dependent kinases-
dc.subjectcyclin-
dc.subjectgenome instability-
dc.subjectmitosis-
dc.titleQuantitative differences between cyclin-dependent kinases underlie the unique functions of CDK1 in human cells-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2021.109808-
dc.identifier.pmid34644583-
dc.identifier.scopuseid_2-s2.0-85116932665-
dc.identifier.volume37-
dc.identifier.issue2-
dc.identifier.spagearticle no. 109808-
dc.identifier.epagearticle no. 109808-
dc.identifier.eissn2211-1247-
dc.identifier.isiWOS:000707017600010-

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