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 language | English (US) |
|---|---|
| Pages (from-to) | 7368-7374 |
| Number of pages | 7 |
| Journal | Nucleic acids research |
| Volume | 40 |
| Issue number | 15 |
| DOIs | |
| State | Published - Aug 2012 |
| Externally published | Yes |
Bibliographical note
Funding Information:National Institutes of Health [R01 CA101864 to Y.W.; R01 ES016114 to L.J.N.; R01 DK071111, R01 DK088561 and P30 DK41296 to S.G.]. This project used the UPCI Transgenic Animal Facility and was supported in part by award [P30CA047904]. Funding for open access charge: NIH [R01 CA101864].