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CDK11p58 kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis

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Abstract

The cyclin-dependent kinase CDK11p58 is specifically expressed at G2/M phase. CDK11p58 depletion leads to different cell cycle defects such as mitotic arrest, failure in centriole duplication and centrosome maturation, and premature sister chromatid separation. We report that upon CDK11 depletion, loss of sister chromatid cohesion occurs during mitosis but not during G2 phase. CDK11p58 depletion prevents Bub1 and Shugoshin 1 recruitment but has no effect on the dimethylation of histone H3 lysine 4 at centromeres. We also report that a construct expressing a kinase dead version of CDK11p58 fails to prevent CDK11 depletion-induced sister chromatid separation, showing that CDK11p58 kinase activity is required for protection of sister chromatid cohesion at centromeres during mitosis. Thus, CDK11p58 kinase activity appears to be involved in early events in the establishment of the centromere protection machinery.

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Abbreviations

CDK11p58 :

Cyclin-dependent kinase 11, p58 isoform

CDK11p110 :

Cyclin-dependent kinase 11, p110 isoform

CREST:

Calcinosis, Raynaud’s phenomenon, esophageal dysmotility, and sclerodactyly telangiectasia

FISH:

Fluorescence in situ hybridization

H2AT120P:

Phosphorylated H2AT120

H3K4diM:

Dimethylated H3K4

H3S10P:

Phosphorylated H3S10

IRES:

Internal ribosomal entry site

PSCS:

Premature sister chromatids separation

SAC:

Spindle assembly checkpoint

siRNA:

Small interference RNA

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Acknowledgments

We are grateful to Yoshinori Watanabe (University of Tokyo, Japan) and Isabelle Bahon-Riedinger (Rennes University Hospital, France) for the gift of reagents and to Erwan Watrin (IGDR, CNRS, Rennes, France) for stimulating helpful discussions. T.R. is supported by a Ligue Contre le Cancer/Région Bretagne fellowship. C.J. is an investigator at the Institut National de la Santé et de la Recherche Médicale (INSERM). Funding was from the French National Research Agency (ANR, project “EpiCentr”), the Région Bretagne (SAD grant), the Cancéropôle Grand-Ouest, the Ligue Contre le Cancer (Comité Grand Ouest), and the Fondation ARC pour la Recherche sur le Cancer.

Conflict of interest

The authors (T.R, C.E., R.G., L.M.-J., and C.J.) declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Institut de Génétique et Développement de Rennes, Equipe Epigénétique et Cancer UMR 6290 CNRS, Université Rennes 1, 35043, Rennes Cedex, France

    Tarik Rakkaa, Laura Magnaghi-Jaulin & Christian Jaulin

  2. UMR7196 MNHN-CNRS, Muséum National d’Histoire Naturelle, 75231, Paris Cedex 05, France

    Christophe Escudé

  3. Institut de Génétique et Développement de Rennes Equipe Cytosquelette et Prolifération Cellulaire UMR 6290 CNRS, Université Rennes 1, 35043, Rennes Cedex, France

    Régis Giet

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  1. Tarik Rakkaa
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  2. Christophe Escudé
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  4. Laura Magnaghi-Jaulin
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  5. Christian Jaulin
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Correspondence to Christian Jaulin.

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Communicated by: Beth A. Sullivan.

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Rakkaa, T., Escudé, C., Giet, R. et al. CDK11p58 kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome Res 22, 267–276 (2014). https://doi.org/10.1007/s10577-013-9400-x

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