Interaction of the p53-Regulated Protein Gadd45 with Proliferating Cell Nuclear Antigen

• Published in: Science (American Association for the Advancement of Science) Vol. 266; no. 5189; pp. 1376 - 1380
• Main Authors: Smith, Martin L., I.-Tsuen Chen, Zhan, Qimin, Bae, Insoo, Chen, Chaw-Yuan, Gilmer, Tona M., Kastan, Michael B., O'Connor, Patrick M., Fornace, Albert J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 25-11-1994; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Biological and medical sciences; Cell cycle, cell proliferation; Cell Division - drug effects; Cell growth; Cell Line; Cell lines; Cell nuclei; Cell nucleus; Cell physiology; Cellular immunity; Chemistry; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cyclins - metabolism; Deoxyribonucleic acid; DNA; DNA - biosynthesis; DNA Damage; DNA Repair; Fundamental and applied biological sciences. Psychology; GADD45 Proteins; Genes; Genes, p53; Humans; Immunoprecipitation; Intracellular Signaling Peptides and Proteins; Logical Thinking; Molecular and cellular biology; Plasmids; Proliferating Cell Nuclear Antigen - metabolism; Proteins - metabolism; Proteins - pharmacology; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; S Phase - drug effects; Somatic cells; Transfection; Tumor Cells, Cultured; Cell proliferation; Molecular association; Regulation(control); Repair; DNA; Biological activity
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7973727

GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21$^{WAF1/CIP1}$, 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.