Structural basis for the inhibition of human alkyladenine DNA by 3,N4-ethenocytosine containing DNA

نویسندگان

  • Gondichatnahalli M. Lingaraju
  • C. Ainsley Davis
  • Jeremy W. Setser
  • Leona D. Samson
  • Catherine L. Drennan
چکیده

Citation Lingaraju, Gondichatnahalli M. et al. “Structural Basis for the Inhibition of Human Alkyladenine DNA Glycosylase (AAG) by 3,N4-Ethenocytosine-containing DNA.” Journal of Biological Chemistry 286.15 (2011) : 13205 -13213. © 2011 by American Society for Biochemistry and Molecular Biology. As Published http://dx.doi.org/10.1074/jbc.M110.192435 Publisher American Society for Biochemistry and Molecular Biology, Inc.

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Structural Basis for the Inhibition of Human Alkyladenine DNA Glycosylase (AAG) by 3,N4-Ethenocytosine-containing DNA*

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Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase.

Exocyclic ethenobases are highly mutagenic DNA lesions strongly implicated in inflammation and vinyl chloride-induced carcinogenesis. While the alkyladenine DNA glycosylase, AAG (or MPG), binds the etheno lesions 1,N(6)-ethenoadenine (ɛA) and 3,N(4)-ethenocytosine (ɛC) with high affinity, only ɛA can be excised to initiate base excision repair. Here, we discover that the human AlkB homolog 2 (A...

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A 55-kDa protein isolated from human cells shows DNA glycosylase activity toward 3,N4-ethenocytosine and the G/T mismatch.

Etheno adducts in DNA arise from multiple endogenous and exogenous sources. Of these adducts we have reported that, 1,N6-ethenoadenine (epsilonA) and 3,N4-ethenocytosine (epsilonC) are removed from DNA by two separate DNA glycosylases. We later confirmed these results by using a gene knockout mouse lacking alkylpurine-DNA-N-glycosylase, which excises epsilonA. The present work is directed towar...

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3,N4-ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase.

Exocyclic DNA adducts are generated in cellular DNA by various industrial pollutants such as the carcinogen vinyl chloride and by endogenous products of lipid peroxidation. The etheno derivatives of purine and pyrimidine bases 3,N4-ethenocytosine (epsilonC), 1, N6-ethenoadenine (epsilonA), N2,3-ethenoguanine, and 1, N2-ethenoguanine cause mutations. The epsilonA residues are excised by the huma...

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تاریخ انتشار 2011