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Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription

Nature Cell Biology volume 13, pages 1450–1456 (2011)Cite this article

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Abstract

Kinases and phosphatases regulate messenger RNA synthesis through post-translational modification of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (ref. 1). In yeast, the phosphatase Cdc14 is required for mitotic exit2,3 and for segregation of repetitive regions4. Cdc14 is also a subunit of the silencing complex RENT (refs 5, 6), but no roles in transcriptional repression have been described. Here we report that inactivation of Cdc14 causes silencing defects at the intergenic spacer sequences of ribosomal genes during interphase and at Y′ repeats in subtelomeric regions during mitosis. We show that the role of Cdc14 in silencing is independent of the RENT deacetylase subunit Sir2. Instead, Cdc14 acts directly on RNA polymerase II by targeting CTD phosphorylation at Ser 2 and Ser 5. We also find that the role of Cdc14 as a CTD phosphatase is conserved in humans. Finally, telomere segregation defects in cdc14 mutants4 correlate with the presence of subtelomeric Y′ elements and can be rescued by transcriptional inhibition of RNA polymerase II.

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Figure 1: Cdc14 is required for rDNA silencing.
Figure 2: Cdc14 is an RNAP-II CTD phosphatase.
Figure 3: Cdc14 represses transcription of subtelomeric Y′ elements.
Figure 4: Cdc14 recruits condensin to telomeres containing Y′ elements.
Figure 5: Segregation of telomeres with Y′-elements requires Cdc14.

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Acknowledgements

We are very grateful to L. Warfield and S. Hahn for advice. We thank D. Morgan (UCSF) and A. Amon (MIT) for reagents. We are grateful to all members of the Aragon laboratory for discussions and comments on the manuscript. The Bueno and Sacristán laboratories are financially supported by grants from the Spanish Science Ministry (MICINN). The Eick laboratory is supported by the Deutsche Forschungsgemeinschaft, SFB-Transregio5. The Aragon and Merkenschlager laboratories are supported by the Medical Research Council (MRC) of the UK.

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Authors and Affiliations

  1. Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK

    Andres Clemente-Blanco, Nicholas Sen, Maria Mayan-Santos, Adam Jarmuz & Luis Aragón

  2. Centro de Investigación del Cáncer, Universidad de Salamanca/CSIC, 37007 Salamanca, Spain

    Maria P. Sacristán & Avelino Bueno

  3. Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK

    Bryony Graham & Matthias Merkenschlager

  4. Genomics Laboratory, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK

    Adam Giess, Elizabeth Webb & Laurence Game

  5. Department of Molecular Epigenetics, Helmholtz-Center Munich, Center of Integrated Protein Science (CIPSM), Marchioninistrasse 25, 81377 Munich, Germany

    Dirk Eick

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  1. Andres Clemente-Blanco
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Contributions

A.C-B. and L.A. conceived the study and analysed the data with critical input from M.M. Experiments were conducted by A.C-B., N.S., M.M-S., A.J. and B.G. Microarray analysis was done by L.G. A.G. and E.W. Critical materials were provided by M.P.S., A.B. and D.E. L.A. wrote the paper and all authors discussed the results and commented on the manuscript.

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Correspondence to Luis Aragón.

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Clemente-Blanco, A., Sen, N., Mayan-Santos, M. et al. Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription. Nat Cell Biol 13, 1450–1456 (2011). https://doi.org/10.1038/ncb2365

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