Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Author Correction: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Profiling of gut microbiota and plasma metabolites in persons with type 1 diabetes and kidney disease

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  3. A distinctive epigenetic ageing profile in human granulosa cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Review of injection techniques for spermatogonial stem cell transplantation

    Research output: Contribution to journalReviewResearchpeer-review

  5. Improving the maturation rate of human oocytes collected ex vivo during the cryopreservation of ovarian tissue

    Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
View graph of relations

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.

Original languageEnglish
JournalNature Communications
Volume6
Pages (from-to)6533
ISSN2041-1723
DOIs
Publication statusPublished - 30 Mar 2015

    Research areas

  • Amino Acid Transport Systems/metabolism, Cell Cycle Checkpoints, Cell Cycle Proteins/genetics, Chaperonin Containing TCP-1/metabolism, Chromatin/metabolism, Chromosomal Proteins, Non-Histone/metabolism, DNA Damage/genetics, DNA-Binding Proteins/metabolism, Genomic Instability, HeLa Cells, Heat-Shock Proteins/metabolism, Humans, Mutation, Phosphoprotein Phosphatases/genetics, Proteasome Endopeptidase Complex, Protein Folding, Proteins/metabolism, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins/genetics, Sumoylation, Ubiquitination

ID: 54999986