hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway

Nucleic Acids Res. 2015 Oct 15;43(18):8817-29. doi: 10.1093/nar/gkv790. Epub 2015 Aug 10.

Abstract

The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Cell Survival
  • Chromatin / enzymology
  • Chromatin / metabolism
  • DNA Adducts / metabolism
  • DNA Glycosylases / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • HeLa Cells
  • Humans
  • Mitochondrial Proteins / metabolism*
  • Mitochondrial Proteins / physiology
  • Oxidative Stress

Substances

  • Chromatin
  • DNA Adducts
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • SSBP1 protein, human
  • 8-hydroxyguanine
  • Guanine
  • Ataxia Telangiectasia Mutated Proteins
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human