A nucleotide excision repair master-switch: p53 regulated coordinate induction of global genomic repair genes.
The tumor suppressor gene p53 is mutated in many human cancers. One of its major roles is as a transcription factor, and its many effector genes control key cellular processes including cell cycle checkpoints and apoptosis. An important role in DNA repair is also emerging for both p53 itself and some of its effector genes. The products of two p53-regulated genes, GADD45a and DDB2, are now known to participate in the global genomic repair (GGR) sub-pathway of nucleotide excision repair (NER). We recently reported the induction of a third GGR gene, XPC, following exposure of normal human peripheral blood lymphocytes to gamma-rays. We now show that XPC is induced in a variety of human cell lines in response to both ionizing and ultra-violet (UV) radiation and alkylating agents, and that this induction requires wild-type p53.
Amundson
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National Institutes of Health, National Cancer Institute, Division of Basic Science, 37 Convent Dr., Bldg. 37, RM. 6144, Bethesda, Maryland 20892, USA. amundson@box-a.nih.gov
Patterson
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Fornace
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D020137:Base Pair Mismatch; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C117669:DDB2 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C086984:XPC protein, human