Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21WAF1/CIP1, whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. Gadd45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results establish GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair.
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.
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Smith
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Chen
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Zhan
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Bae
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Chen
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Gilmer
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Kastan
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O'Connor
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Fornace
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004260:DNA Repair; D016158:Genes, p53; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004247:DNA; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011994:Recombinant Proteins; D000097642:GADD45 Proteins; C493956:CDKN1A protein, human