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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication

Anna Mosbech1, Ian Gibbs-Seymour, Konstantinos Kagias

  • 1Ubiquitin Signaling Group, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Nature Structural & Molecular Biology
|October 9, 2012
PubMed

Insights

Human DVC1 protein acts as a DNA damage sensor, recruiting the p97 chaperone to stalled replication forks. This process is crucial for DNA repair and preventing mutations caused by replication stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Ubiquitin signaling is essential for DNA damage response and repair.
  • Replication stress can lead to genomic instability if not properly managed.

Purpose of the Study:

  • To identify and characterize the function of human DVC1 (also known as C1orf124 or Spartan) in DNA damage response pathways.
  • To elucidate the mechanism by which DVC1 interacts with other proteins to resolve replication stress.

Main Methods:

  • Cell cycle analysis and immunofluorescence to track DVC1 localization.
  • Biochemical assays to study protein-protein interactions (DVC1, p97, PCNA).
  • Functional assays using gene knockdown and sensitivity tests to DNA damaging agents.

Main Results:

  • DVC1 accumulates at stalled replication forks during replication stress.
  • DVC1's recruitment depends on its UBZ domain and PIP box but not PCNA monoubiquitylation.
  • DVC1 acts as a scaffold, recruiting the p97 chaperone via its SHP box to facilitate the removal of translesion synthesis polymerase η (Pol η).
  • DVC1 depletion increases UV-induced mutagenesis and causes hypersensitivity to replication stress agents.

Conclusions:

  • DVC1 functions as a DNA damage-targeting p97 adaptor protein.
  • DVC1 plays a critical role in protecting cells from replication blocks and associated mutagenesis.
  • The p97 chaperone is implicated in the ubiquitin-dependent regulation of translesion synthesis.

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