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.
Smith
M L
ML
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.
Chen
I T
IT
Zhan
Q
Q
Bae
I
I
Chen
C Y
CY
Gilmer
T M
TM
Kastan
M B
MB
O'Connor
P M
PM
Fornace
A J
AJ
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