title: Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion.
abstract: Exposure to reactive oxygen species (ROS) can give rise to the formation of various DNA damage products. Among them, d(G[8-5 m]T) can be induced in isolated DNA treated with Fenton reagents and in cultured human cells exposed to γ-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.
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521-0403, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Huachuan
authors.initials: H
authors.lastname: Cao
authors.forename: Changjun
authors.initials: C
authors.lastname: You
authors.forename: Bifeng
authors.initials: B
authors.lastname: Yuan
authors.forename: Ralf
authors.initials: R
authors.lastname: Bahde
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Brooks
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D051381:Rats; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*
chemical_list: C576135:G(8-5m)T; D006147:Guanine; D004247:DNA; D013941:Thymine