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

doi:10.1093/nar/gks357

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

Medicine

Research output: Contribution to journal › Article › peer-review

35 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 language	English (US)
Pages (from-to)	7368-7374
Number of pages	7
Journal	Nucleic acids research
Volume	40
Issue number	15
DOIs	https://doi.org/10.1093/nar/gks357
State	Published - Aug 2012

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/nar/gks357

Cite this

@article{761b98f091c64bd99cafe2090cdd3dbe,

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

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.",

author = "Jin Wang and Huachuan Cao and Changjun You and Bifeng Yuan and Ralf Bahde and Sanjeev Gupta and Chikako Nishigori and Niedernhofer, {Laura J.} and Brooks, {Philip J.} and Yinsheng Wang",

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].",

year = "2012",

month = aug,

doi = "10.1093/nar/gks357",

language = "English (US)",

volume = "40",

pages = "7368--7374",

journal = "Nucleic acids research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "15",

}

TY - JOUR

T1 - Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion

AU - Wang, Jin

AU - Cao, Huachuan

AU - You, Changjun

AU - Yuan, Bifeng

AU - Bahde, Ralf

AU - Gupta, Sanjeev

AU - Nishigori, Chikako

AU - Niedernhofer, Laura J.

AU - Brooks, Philip J.

AU - Wang, Yinsheng

N1 - 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].

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84867322556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867322556&partnerID=8YFLogxK

U2 - 10.1093/nar/gks357

DO - 10.1093/nar/gks357

M3 - Article

C2 - 22581771

AN - SCOPUS:84867322556

SN - 0305-1048

VL - 40

SP - 7368

EP - 7374

JO - Nucleic acids research

JF - Nucleic acids research

IS - 15

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this