Fortini P, Pascucci B, Parlanti E, D'Errico M, Simonelli V, Dogliotti E
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Biochimie. 2003 Nov;85(11):1053-71. doi: 10.1016/j.biochi.2003.11.003.
Base damage or loss occurs at high frequency in the cells (almost 10(4) bases are damaged and hydrolysed per cell per day). DNA repair is fundamental to maintain genomic integrity. Base excision repair (BER) is the main mechanism by which cells correct various types of damaged DNA bases generated either by endogenous or exogenous factors. The widely accepted model for BER mechanism involves five sequential reactions: (i) base removal; (ii) incision of the resulting abasic site; (iii) processing of the generated termini at the strand break; (iv) DNA synthesis, and (v) ligation. In this review, we will briefly summarise the biochemistry of each BER step and will concentrate on the biological relevance of BER as inferred from in vitro and in vivo studies. This information will be the basis for speculation on the potential role of malfunction of BER in human pathology.
碱基损伤或丢失在细胞中高频发生(每个细胞每天约有10⁴个碱基被损伤和水解)。DNA修复对于维持基因组完整性至关重要。碱基切除修复(BER)是细胞纠正由内源性或外源性因素产生的各种类型受损DNA碱基的主要机制。被广泛接受的BER机制模型涉及五个连续反应:(i)碱基切除;(ii)对产生的无碱基位点进行切割;(iii)处理链断裂处产生的末端;(iv)DNA合成,以及(v)连接。在本综述中,我们将简要总结BER每个步骤的生物化学过程,并将重点关注从体外和体内研究推断出的BER的生物学意义。这些信息将成为推测BER功能异常在人类病理学中潜在作用的基础。