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p53与核苷酸切除修复过程中DNA损伤识别的调控

p53 and regulation of DNA damage recognition during nucleotide excision repair.

作者信息

Adimoolam Shanthi, Ford James M

机构信息

Department of Medicine (Oncology), Stanford University School of Medicine, 1115 CCSR Building, 269 Campus Drive, Stanford, CA 94305, USA.

出版信息

DNA Repair (Amst). 2003 Sep 18;2(9):947-54. doi: 10.1016/s1568-7864(03)00087-9.

Abstract

In response to a variety of types of DNA damage, the p53 tumor suppressor gene product is activated and regulates a number of downstream cellular processes such as cell cycle arrest, apoptosis and DNA repair. Recent discoveries concerning the regulation of DNA repair processes by p53, such as nucleotide excision repair (NER) and base excision repair (BER) have paved the way for studies to understand the mechanisms governing p53-dependent DNA repair. Although several theories have been proposed, accumulating evidence points to a transcriptional regulatory role for p53 in NER, mediating expression of the global genomic repair (GGR)-specific damage recognition genes, DDB2 and XPC. In BER, a more direct role for p53 has been proposed, potentially acting through protein-protein interactions with BER specific factors. These advances have greatly enhanced our understanding of the role of p53 in DNA repair and this review comprehensively summarizes current opinions on the mechanisms of p53-dependent DNA repair.

摘要

针对多种类型的DNA损伤,p53肿瘤抑制基因产物被激活,并调节许多下游细胞过程,如细胞周期停滞、细胞凋亡和DNA修复。最近关于p53对DNA修复过程的调控的发现,如核苷酸切除修复(NER)和碱基切除修复(BER),为理解p53依赖性DNA修复的机制的研究铺平了道路。尽管已经提出了几种理论,但越来越多的证据表明p53在NER中具有转录调节作用,介导全局基因组修复(GGR)特异性损伤识别基因DDB2和XPC的表达。在BER中,有人提出p53具有更直接的作用,可能通过与BER特异性因子的蛋白质-蛋白质相互作用发挥作用。这些进展极大地增进了我们对p53在DNA修复中的作用的理解,本综述全面总结了目前关于p53依赖性DNA修复机制的观点。

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