USP7/HAUSP Stimulates Repair of Oxidative DNA Lesions

Nucleic Acids Res. 2011 Apr;39(7):2604-9. doi: 10.1093/nar/gkq1210. Epub 2010 Dec 7.

Abstract

USP7 is involved in the cellular stress response by regulating Mdm2 and p53 protein levels following severe DNA damage. In addition to this, USP7 may also play a role in chromatin remodelling by direct deubiquitylation of histones, as well as indirectly by regulating the cellular levels of E3 ubiquitin ligases involved in histone ubiquitylation. Here, we provide new evidence that USP7 modulated chromatin remodelling is important for base excision repair of oxidative lesions. We show that transient USP7 siRNA knockdown did not change the levels or activity of base excision repair enzymes, but significantly reduced chromatin DNA accessibility and consequently the rate of repair of oxidative lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • DNA Damage
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • HeLa Cells
  • Humans
  • Oxidation-Reduction
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA Interference
  • Ubiquitin Thiolesterase / antagonists & inhibitors
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitin Thiolesterase / physiology*
  • Ubiquitin-Specific Peptidase 7

Substances

  • Chromatin
  • Proto-Oncogene Proteins c-mdm2
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7
  • DNA Repair Enzymes