Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
Trends Biochem Sci. 2012 Apr;37(4):162-72. doi: 10.1016/j.tibs.2011.12.002. Epub 2012 Jan 27.
The expansion of trinucleotide repeat (TNR) sequences in human DNA is considered to be a key factor in the pathogenesis of more than 40 neurodegenerative diseases. TNR expansion occurs during DNA replication and also, as suggested by recent studies, during the repair of DNA lesions produced by oxidative stress. In particular, the oxidized guanine base 8-oxoguanine within sequences containing CAG repeats may induce formation of pro-expansion intermediates through strand slippage during DNA base excision repair (BER). In this article, we describe how oxidized DNA lesions are repaired by BER and discuss the importance of the coordinated activities of the key repair enzymes, such as DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase, in preventing strand slippage and TNR expansion.
三核苷酸重复(TNR)序列在人类 DNA 中的扩展被认为是 40 多种神经退行性疾病发病机制的关键因素。TNR 扩展发生在 DNA 复制过程中,最近的研究还表明,它也发生在由氧化应激产生的 DNA 损伤修复过程中。特别是,在含有 CAG 重复序列的碱基中,氧化的鸟嘌呤碱基 8-氧鸟嘌呤可能会通过 DNA 碱基切除修复(BER)过程中的链滑动诱导前扩展中间体的形成。在本文中,我们描述了氧化的 DNA 损伤如何通过 BER 修复,并讨论了关键修复酶,如 DNA 聚合酶 β、核酸内切酶 1(FEN1)和 DNA 连接酶的协调活动,在防止链滑动和 TNR 扩展方面的重要性。