Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

Bruner, Steven D.; Norman, Derek P. G.; Verdine, Gregory L.

doi:10.1038/35002510

Cited by 916 publications

(1,066 citation statements)

References 43 publications

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“…8-oxodG is known to cause DNA misreplication resulting in mutation or cancer (19,20). Catechol increased the amount of 8-oxodG in HL-60, whereas the amount of 8-oxodG in HP100 was not increased.…”

Section: The Role Of Reactive Oxygen Species In Carcinogenesismentioning

confidence: 96%

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Oikawa

2005

Environ Health Prev Med

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Reactive oxygen species (ROS) generated by environmental chemicals can cause sequence-specific DNA damage, which may lead to carcinogenesis and aging. We investigated the mechanism of DNA damage by environmental chemicals (catechol, propyl gallate and bisphenol-A), homocysteine and UVA radiation using human cultured cell lines and 32 P-labeled DNA fragments. Carcinogenic catechol induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II) and NADH. Furthermore, catechol increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, but not in HP100, a hydrogen peroxide (H 2 O 2 )-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H 2 O 2 plays an important role in the carcinogenic process of catechol. In addition, an environmental factor, bisphenol-A, and a dietary factor, propyl gallate, also induced sequence-specific DNA damage via ROS generation.UVA, as well as UVB, contributes to photoaging. In humans, telomere shortening is believed to be associated with cell senescence. In this study, we investigated the shortening rate of telomeres in human WI-38 fibroblasts exposed to UVA irradiation. The telomere length (as measured by terminal restriction fragment length) in WI-38 fibroblasts irradiated with UVA decreased with increasing the irradiation dose. UVA irradiation with riboflavin caused damage specifically at the GGG sequence in the DNA fragments containing telomere sequence (TTAGGG) 4 . We concluded that the GGG-specific damage in telomere sequence induced by UVA irradiation participates in the increase of the telomere shortening rate.In this report, we show our experimental results and discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging.

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Section: The Role Of Reactive Oxygen Species In Carcinogenesismentioning

confidence: 96%

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Oikawa

2005

Environ Health Prev Med

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“…Formation of 8-oxodG causes DNA misreplication, which can lead to mutation, particularly G3 T substitution. 14,15 To investigate whether estrogens and their metabolites are more important in tumor promotion, we examined the effects of estradiol and catechol estrogens on proliferation of estrogen-dependent MCF-7 cells, derived from human breast-cancer cells.…”

mentioning

confidence: 99%

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

et al. 2001

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Estrogen-induced carcinogenesis involves enhanced cell proliferation (promotion) and genotoxic effects (initiation).To investigate the contribution of estrogens and their metabolites to tumor initiation, we examined DNA damage induced by estradiol and its metabolites, the catechol estrogens 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ). In the presence of Cu(II), catechol estrogens formed piperidine-labile sites at thymine and cytosine residues in 32 P 5 -end-labeled DNA fragments and induced the formation of 8-oxo-7, Epidemiological studies and animal experiments have revealed that estrogens are carcinogenic. 1 In humans, elevated circulating estrogen levels, caused either by increased endogenous hormone production or by therapeutic doses of estrogen medications, increase breast and uterine cancer risk. 2 Prolonged exposure of women to high estrogen levels is associated with an elevated incidence of breast cancer. 3 Administration of estradiol to mice increased the incidence of mammary, pituitary, uterine, cervical, vaginal, testicular, lymphoid and bone tumors. 2,4 In rats, estrogen increased the incidence of mammary and/or pituitary tumors. 2,5 Estrogens can cause cancer by stimulating cell proliferation and causing genotoxic damage. 6,7 Estrogens are highly mitogenic in hormone-sensitive tissues, such as the uterus and breast. 8 Prolonged exposure of target tissues and cells to excessive mitogenic stimulation by estrogens has been considered an important etiological factor for the induction of estrogen-associated cancers in experimental animals and humans. 8 Thus, estrogens are considered to participate in tumor promotion.However, estrogens have been reported to cause cancer through their genotoxic effects. Estradiol caused sister chromatid exchanges and chromosomal aberrations in peripheral blood human lymphocyte culture, and metabolic activation enhanced these chromosomal lesions. 9 Catechol estrogens are also capable of causing chromosomal aberrations and gene mutations in cultured cells. 10 Thus, the genotoxic effects of estradiol could result from accumulation of potentially carcinogenic metabolites. Estradiol undergoes cytochrome P-450 -catalyzed hydroxylation to various catechol estrogens. 8 2-Hydroxylation is a major metabolic pathway in the liver, whereas 4-hydroxylation dominates in extrahepatic organs susceptible to estrogens. 8,11,12 Catechol estrogens show much more potent carcinogenic effects on mice than estradiol. 13 Therefore, catechol estrogens can be potent carcinogens and may participate in tumor initiation by causing DNA damage.To investigate the role of catechol estrogens in tumor initiation, we examined DNA damage induced by 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ) using 32 P 5Ј-end-labeled DNA fragments obtained from the human p53 tumor-suppressor gene and the c-Ha-ras-1 proto-oncogene. We also measured the formation of 8-oxo-7,8-dihydro-2Ј-deoxyguanosine (8-oxodG), an indicator of oxidative damage to DNA, using an electrochemical detector coup...

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“…The hOGG1 molecule can recognize 8-OHdG, and then catalyse both the release of 8-OHdG and the cleavage of DNA at the resulting apurinic site. 21 The enzyme itself is very sensitive to UVB irradiation, which causes photolysis of tryptophan residues at the active site and leads to hOGG1 inactivation. 30 It has been demonstrated that a CG polymorphism at nucleotide position 1245 in exon 7 of the hOGG1 gene results in an amino-acid substitution from serine to cysteine at residue 326.…”

Section: Discussionmentioning

confidence: 99%

“…The human 8-oxoguanine glycosylase I (hOGG1) is the key component responsible for the removal of 8-OHdG in DNA. 21 Previous genetic studies have revealed the presence of several polymorphisms within the hOGG1 locus. 22,23 Among them, a common polymorphism has been shown to have a functional difference.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese

Hc¹,

Cc²,

Wm³

et al. 2004

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Purpose Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2 0 -deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. Methods In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by w 2 -test and logistic regression. Results The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/ Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P ¼ 0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P ¼ 0.025). Conclusions Our findings suggest that the 1245C-G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.

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Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

Cited by 916 publications

References 43 publications

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese

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