Physical and functional interaction between WRNIP1 and RAD18

Genes Genet Syst. 2009 Apr;84(2):171-8. doi: 10.1266/ggs.84.171.

Abstract

WRN interacting protein 1 (WRNIP1) was originally identified as a protein that interacts with the Werner syndrome responsible gene product (WRN). WRNIP1 is a highly conserved protein from E. coli to humans. Genetic studies in budding yeast suggested that the yeast orthlog of WRNIP1, Mgs1, may function in a DNA damage tolerance pathway that is similar to, but distinct from, the template-switch damage avoidance pathway involving Rad6, Rad18, Rad5, Mms2, and Ubc13. Here we report that human WRNIP1 binds in an ATP dependent manner to both forked DNA that mimics stalled replication forks and to template/primer DNA. We found that WRNIP1 interacts physically with RAD18 and interferes with the binding of RAD18 to forked DNA and to template/primer DNA. In contrast, RAD18 enhances the binding of WRNIP1 to these DNAs, suggesting that WRNIP1 targets DNA bound by RAD18.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphate / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Immunoprecipitation
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Spodoptera
  • Transfection
  • Ubiquitin-Protein Ligases

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Oligonucleotides
  • RAD18 protein, human
  • Adenosine Triphosphate
  • Ubiquitin-Protein Ligases
  • WRNIP1 protein, human
  • ATPases Associated with Diverse Cellular Activities