title: Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control.
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.
authors: Department of Biology, University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark.
authors: Irene
authors: I
authors: Gallina
authors: Department of Biology, University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark.
authors: Camilla
authors: C
authors: Colding
authors: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N DK-2200, Denmark.
authors: Peter
authors: P
authors: Henriksen
authors: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N DK-2200, Denmark.
authors: Petra
authors: P
authors: Beli
authors: Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen N DK-2200, Denmark.
authors: Kyosuke
authors: K
authors: Nakamura
authors: MRC, Centre for Genome Damage and Stability, School of Life Sciences, University of Sussex, Brighton BN1 9RH, UK.
authors: Judith
authors: J
authors: Offman
authors: Department of Biology, University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark.
authors: David P
authors: DP
authors: Mathiasen
authors: Department of Biology, University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark.
authors: Sonia
authors: S
authors: Silva
authors: MRC, Centre for Genome Damage and Stability, School of Life Sciences, University of Sussex, Brighton BN1 9RH, UK.
authors: Eva
authors: E
authors: Hoffmann
authors: Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen N DK-2200, Denmark.
authors: Anja
authors: A
authors: Groth
authors: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N DK-2200, Denmark.
authors: Chunaram
authors: C
authors: Choudhary
authors: Department of Biology, University of Copenhagen, Room 4.1.07, Copenhagen N DK-2200, Denmark.
authors: Michael
authors: M
authors: Lisby
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D056404:Chaperonin Containing TCP-1 / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042822:Genomic Instability; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D054875:Ubiquitination; D033921:Vesicular Transport Proteins; D050888:Heat-Shock Proteins, Small
chemical_list: D026905:Amino Acid Transport Systems; D018797:Cell Cycle Proteins; D056404:Chaperonin Containing TCP-1; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D010749:Phosphoprotein Phosphatases; D046988:Proteasome Endopeptidase Complex; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C473804:BTN2 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D050888:Heat-Shock Proteins, Small; C092693:CTF18 protein, S cerevisiae; C573119:Cmr1 protein, S cerevisiae; C098005:HSP42 protein, S cerevisiae; C441579:MRC1 protein, S cerevisiae; C000606100:WDR76 protein, human; C502440:PPH3 protein, S cerevisiae