Gallina I~Lisby M, 2015

Pubmed ID 25817432
Title Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control.
Authors 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
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.
Citation Nat Commun 2015; 6:6533

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Gallina I~Lisby M, 2015 mutation frequency (CanR) expression of hMLH1 SC - Leu + canavanine ~4,800 None

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