Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion

Jin Wang, Huachuan Cao, Changjun You, Bifeng Yuan, Ralf Bahde, Sanjeev Gupta, Chikako Nishigori, Laura J. Niedernhofer, Philip J. Brooks, Yinsheng Wang

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

SExposure to reactive oxygen species (ROS) can give rise to the formation of various DNA damage products. Among them, d(G[8-5m]T) can be induced in isolated DNA treated with Fenton reagents and in cultured human cells exposed to c-rays, d(G[8-5m]T) can be recognized and incised by purified Escherichia coli UvrABC nuclease. However, it remains unexplored whether d(G[8-5 m]T) accumulates in mammalian tissues and whether it is a substrate for nucleotide excision repair (NER) in vivo. Here, we found that d(G[8-5 m]T) could be detected in DNA isolated from tissues of healthy humans and animals, and elevated endogenous ROS generation enhanced the accumulation of this lesion in tissues of a rat model of Wilson's disease. Additionally, XPA-deficient human brain and mouse liver as well as various types of tissues of ERCC1-deficient mice contained higher levels of d(G[8-5 m]T) but not ROS-induced single-nucleobase lesions than the corresponding normal controls. Together, our studies established that d(G[8-5 m]T) can be induced endogenously in mammalian tissues and constitutes a substrate for NER in vivo.

Original languageEnglish (US)
Pages (from-to)7368-7374
Number of pages7
JournalNucleic acids research
Volume40
Issue number15
DOIs
StatePublished - Aug 2012
Externally publishedYes

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