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First published online July 2, 2007
doi: 10.1242/10.1242/jcs.007963

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CDK11^p58 is required for the maintenance of sister chromatid cohesion

Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA

^* Author for correspondence (e-mail: Jill.Lahti{at}stjude.org)

Accepted 15 May 2007

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.

Key words: CDK11^p58, Cell cycle, Mitosis, Cyclin-dependent kinase, Sister chromatid cohesion, Cohesin, Mouse

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