CDK11(p58) is required for the maintenance of sister chromatid cohesion.
Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11(p110)) throughout the cell cycle and a 58-kDa protein (CDK11(p58)) that is specifically translated from an internal ribosome entry site sequence during G2/M. CDK11(p110) is involved in transcription and RNA processing, and CDK11(p58) is involved in centrosome maturation and spindle morphogenesis. Deletion of the CDK11 gene in mice leads to embryonic lethality at E3.5, and CDK11-deficient blastocysts exhibit both proliferative defects and mitotic arrest. Here we used hypomorphic small interfering RNAs (siRNAs) to demonstrate that, in addition to playing a role in spindle formation and structure, CDK11(p58) is also required for sister chromatid cohesion and the completion of mitosis. Moderate depletion of CDK11 causes misaligned and lagging chromosomes but does not prevent mitotic progression. Further diminution of CDK11 caused defective chromosome congression, premature sister chromatid separation, permanent mitotic arrest and cell death. These cells exhibited altered Sgo1 localization and premature dissociation of cohesion complexes. This severe phenotype was not corrected by codepletion of CDK11 and either Plk1 or Sgo1, but it was rescued by CDK11(p58). These findings are consistent with the mitotic arrest we observed in CDK11-deficient mouse embryos and establish that CDK11(p58) is required for the maintenance of chromosome cohesion and the completion of mitosis.
Hu
Dongli
D
Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Valentine
Marcus
M
Kidd
Vincent J
VJ
Lahti
Jill M
JM
D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002842:Chromatids / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D018816:Genes, cdc; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C496644:SGO1 protein, human; C447612:CDK11a protein, human