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KMID : 0578320000100060723
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Molecules and Cells
2000 Volume.10 No. 6 p.723 ~ p.727
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Excision repair of 2,5-diaziridinyl-1,4-benzoquinone (DZQ)-DNA adduct by bacterial and mammalian 3-methyladenine-DNA glycosylases
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이종순:Lee Chong-Soon
저자없음:No authors listed
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Abstract
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The mechanisms of anticancer activity of 2,5-diaziridinyl- 1,4-benzoquinone (DZQ) are believed to involve the alkylation of guanine and adenine bases. In this study, it has been investigated whether bacterial and mammalian 3-methyladenine-DNA glycosylases are able to excise DZQ-DNA adduct with a differential substrate specificity. DZQ-induced DNA adduct was first formed in the radiolabeled restriction enzyme DNA fragment, and excision of the DNA adduct was analyzed following treatment with homogeneous 3-methyladenine-DNA glycosylase from E. coli, rat, and human, respectively. Abasic sites generated by DNA glycosylases were cleaved by the associated lyase activity of the E. coli formamidopyrimidine- DNA glycosylase. Resolution of cleaved DNA on a sequencing gel with Maxam-Gilbert sequencing reactions showed that DZQ-induced adenine and guanine adducts were very good substrates for bacterial and mammalian enzymes. The E. coli enzyme excises DZQ-induced adenine and guanine adducts with similar efficiency. The rat and human enzymes, however, excise the adenine adduct more efficiently than the guanine adduct. These results suggest that the 3-methyladenineDNA glycosylases from different origins have differential substrate specificity to release DZQ-DNA lesions. The use of 3 methyladenine-DNA glycosylase incision analysis could possibly be applied to quantify a variety of DNA adducts at the nucleotide level.
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KEYWORD
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Anticancer Agent, Adiaziridinylbenzoquinone, Base Excision Repair, Drug-DNA Adduct, 3-Methyl-adenine-DNA Glycosylase
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