Smith M L, Chen I T, Zhan Q, Bae I, Chen C Y, Gilmer T M, Kastan M B, O'Connor P M, Fornace A J
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.
Science. 1994 Nov 25;266(5189):1376-80. 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, 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.
GADD45是一种在哺乳动物中普遍表达的基因,可由DNA损伤及其他某些应激诱导产生。另一个受p53调控的基因p21WAF1/CIP1,其产物可与细胞周期蛋白依赖性激酶(Cdk)及增殖细胞核抗原(PCNA)结合,GADD45与生长抑制有关。研究发现Gadd45可与PCNA结合,PCNA是Cdk复合物的正常组成成分,也是一种参与DNA复制和修复的蛋白质。Gadd45在体外可刺激DNA切除修复,并抑制细胞进入S期。这些结果表明GADD45是p53依赖的细胞周期检查点与DNA修复之间的一个连接点。