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Hsk1–Dfp1 is required for heterochromatin-mediated cohesion at centromeres

Nature Cell Biology volume 5, pages 1111–1116 (2003)Cite this article

Abstract

Heterochromatin performs a central role in chromosome segregation and stability by promoting cohesion at centromeres1,2. Establishment of both heterochromatin-mediated silencing and cohesion requires passage through S phase, although the mechanism is unknown3,4. Here we demonstrate that Schizosaccharomyces pombe Hsk1 (CDC7), a conserved Dbf4-dependent protein kinase (DDK) that regulates replication initiation5, interacts with and phosphorylates the heterochromatin protein 1 (HP1) equivalent Swi6 (ref. 6). Hsk1 and its regulatory subunit Dfp1 function downstream of Swi6 localization to promote heterochromatin function and cohesion specifically at centromeres. This role for Hsk1–Dfp1 is separable from its replication initiation activity, providing a temporal link between S phase and centromere cohesion that is mediated by heterochromatin.

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Figure 1: Hsk1–Dfp1 interacts with and phosphorylates Swi6.
Figure 2: S-phase activity of Hsk1–Dfp1 is required for equal chromosome segregation.
Figure 3: Hsk1–Dfp1 functions downstream of Swi6 localization.
Figure 4: Cohesion at centromeres requires Dfp1.

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Acknowledgements

We are especially grateful to G.W. Brown for communicating results before publication, for providing dfp1 strains and for the Hsk1 kinase assay protocol. We thank H.-K. Huang for the Rad21 plasmid, J.-P. Javerzat for cosmids, and J. Partridge for RT-PCR protocols. We thank our colleagues in the Molecular and Cell Biology Laboratory for discussion and comments on the manuscript. J.M.B. was supported by the Damon Runyon Cancer Research Foundation, fellowship DRG-1634. P.B. was funded by a Wellcome Trust Travelling Research Fellowship, l′ Association pour la Recherche sur le Cancer, la Ligue Nationale Contre le Cancer and the Centre National de la Recherche Scientifique. R.C.A. is a Wellcome Trust Principal Research Fellow funded by EC RTN Contract: ERBFMRXCT980212 and core funding from the Medical Research Council, UK. This work was supported by American Cancer Society grant RSG-00-132-04-CCG and a Stohlman Scholarship from the Leukemia and Lymphoma Society to S.L.F.

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Authors and Affiliations

  1. Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Julie M. Bailis & Susan L. Forsburg

  2. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    Pascal Bernard, Richard Antonelli & Robin C. Allshire

  3. Institut de Biochimie et Génétique Cellulaires, CNRS, Unité Mixte de Recherche 5095, 1 Rue Camille Saint Saëns, Bordeaux, 33077, Cedex, France

    Pascal Bernard

  4. The Wellcome Trust Centre for Cell Biology, ICMB, University of Edinburgh, The King's Buildings, Edinburgh, EH9 3JR, UK

    Richard Antonelli & Robin C. Allshire

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Correspondence to Susan L. Forsburg.

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Bailis, J., Bernard, P., Antonelli, R. et al. Hsk1–Dfp1 is required for heterochromatin-mediated cohesion at centromeres. Nat Cell Biol 5, 1111–1116 (2003). https://doi.org/10.1038/ncb1069

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