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

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posted on 2023-06-08, 21:18 authored by Irene Gallina, Camilla Colding, Peter Henriksen, Petra Beli, Kyosuke Nakamura, Judith Muriel Offman, David Mathiasen, Sonia Silva, Eva Hoffmann, Anja Groth, Chunaram Choudhary, Michael Lisby
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nature Communications

ISSN

2041-1723

Publisher

Nature

Volume

6

Page range

6533

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-06-29

First Open Access (FOA) Date

2015-07-01

First Compliant Deposit (FCD) Date

2015-06-29

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