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

Gallina, Irene, Colding, Camilla, Henriksen, Peter, Beli, Petra, Nakamura, Kyosuke, Offman, Judith Muriel, Mathiasen, David, Silva, Sonia, Hoffmann, Eva, Groth, Anja, Choudhary, Chunaram and Lisby, Michael (2015) Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control. Nature Communications, 6. p. 6533. ISSN 2041-1723

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Nikoleta Kiapidou
Date Deposited: 29 Jun 2015 12:56
Last Modified: 07 Mar 2017 06:13
URI: http://sro.sussex.ac.uk/id/eprint/55032

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