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Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

Author

Listed:
  • Irene Gallina

    (University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark)

  • Camilla Colding

    (University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark)

  • Peter Henriksen

    (The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Petra Beli

    (The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Present address: Institute of Molecular Biology (IMB), 55128 Mainz, Germany)

  • Kyosuke Nakamura

    (Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen)

  • Judith Offman

    (MRC, Centre for Genome Damage and Stability, School of Life Sciences, University of Sussex
    Present address:Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK)

  • David P. Mathiasen

    (University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark)

  • Sonia Silva

    (University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark)

  • Eva Hoffmann

    (MRC, Centre for Genome Damage and Stability, School of Life Sciences, University of Sussex)

  • Anja Groth

    (Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen)

  • Chunaram Choudhary

    (The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Michael Lisby

    (University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark)

Abstract

DNA replication stress is a source of genomic instability. Here we identify changed mutation rate 1 (Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that Cmr1—together with Mrc1/Claspin, Pph3, the chaperonin containing TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to Cmr1, its human orthologue WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that Cmr1/WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins.

Suggested Citation

  • Irene Gallina & Camilla Colding & Peter Henriksen & Petra Beli & Kyosuke Nakamura & Judith Offman & David P. Mathiasen & Sonia Silva & Eva Hoffmann & Anja Groth & Chunaram Choudhary & Michael Lisby, 2015. "Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control," Nature Communications, Nature, vol. 6(1), pages 1-16, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7533
    DOI: 10.1038/ncomms7533
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    Cited by:

    1. Arun Kumar & Veena Mathew & Peter C. Stirling, 2024. "Dynamics of DNA damage-induced nuclear inclusions are regulated by SUMOylation of Btn2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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