p53 modulation of TFIIH-associated nucleotide excision repair activity.
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.
Wang
X W
XW
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Yeh
H
H
Schaeffer
L
L
Roy
R
R
Moncollin
V
V
Egly
J M
JM
Wang
Z
Z
Freidberg
E C
EC
Evans
M K
MK
Taffe
B G
BG
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D003057:Cockayne Syndrome / Q000201:enzymology / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009711:Nucleotides; D000075223:Poly-ADP-Ribose Binding Proteins; D017433:Protein Structure, Secondary; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D019473:Transcription Factors, TFII; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D009711:Nucleotides; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D016159:Tumor Suppressor Protein p53; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D000251:Adenosine Triphosphatases; C061897:Rad3 protein, S cerevisiae; D004265:DNA Helicases; C078673:ERCC6 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes