p53 modulation of TFIIH-associated nucleotide excision repair activity

Nat Genet. 1995 Jun;10(2):188-95. doi: 10.1038/ng0695-188.

Abstract

p53 has pleiotropic functions including control of genomic plasticity and integrity. Here we report that p53 can bind to several transcription factor IIH-associated factors, including transcription-repair factors, XPD (Rad3) and XPB, as well as CSB involved in strand-specific DNA repair, via its C-terminal domain. We also found that wild-type, but not Arg273His mutant p53 inhibits XPD (Rad3) and XPB DNA helicase activities. Moreover, repair of UV-induced dimers is slower in Li-Fraumeni syndrome cells (heterozygote p53 mutant) than in normal human cells. Our findings indicate that p53 may play a direct role in modulating nucleotide excision repair pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Chromosome Mapping
  • Cockayne Syndrome / enzymology
  • Cockayne Syndrome / genetics
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Humans
  • Li-Fraumeni Syndrome / enzymology
  • Li-Fraumeni Syndrome / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleotides
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Secondary
  • Proteins / genetics
  • Proteins / metabolism
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor TFIIH
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcription Factors, TFII*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA-Binding Proteins
  • Nucleotides
  • Poly-ADP-Ribose Binding Proteins
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Transcription Factors, TFII
  • Tumor Suppressor Protein p53
  • XPBC-ERCC-3 protein
  • Transcription Factor TFIIH
  • Adenosine Triphosphatases
  • Rad3 protein, S cerevisiae
  • DNA Helicases
  • ERCC6 protein, human
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • DNA Repair Enzymes