1,N6-α-hydroxypropanoadenine, the acrolein adduct to adenine, is a substrate for AlkB dioxygenase
نویسندگان
چکیده
منابع مشابه
Mechanism of Repair of Acrolein- and Malondialdehyde-Derived Exocyclic Guanine Adducts by the α-Ketoglutarate/Fe(II) Dioxygenase AlkB
The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M1dG are formed when DNA is exposed to the reactive aldehydes acrolein and malondialdehyde (MDA). These lesions are believed to form the basis for the observed cytotoxicity and mutagenicity of acrolein and MDA. In an effort to understand the enzymatic pathways and chemical mech...
متن کاملMinimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase.
The Escherichia coli AlkB protein, and two human homologs ABH2 and ABH3, directly demethylate 1-methyladenine and 3-methylcytosine in DNA. They couple Fe(II)-dependent oxidative demethylation of these damaged bases to decarboxylation of alpha-ketoglutarate. Here, we have determined the kinetic parameters for AlkB oxidation of 1-methyladenine in poly(dA), short oligodeoxyribonucleotides, nucleot...
متن کاملSolution structure of DNA containing α-OH-PdG: the mutagenic adduct produced by acrolein
Acrolein is a cell metabolic product and a main component of cigarette smoke. Its reaction with DNA produces two guanine lesions gamma-OH-PdG, a major adduct that is nonmutagenic in mammalian cells, and the positional isomer alpha-OH-PdG. We describe here the solution structure of a short DNA duplex containing a single alpha-OH-PdG lesion, as determined by solution NMR spectroscopy and restrain...
متن کاملExocyclic Carbons Adjacent to the N6 of Adenine are Targets for Oxidation by the Escherichia coli Adaptive Response Protein AlkB
The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- and α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as AlkB targets, earlier work suggests that the initial target of oxidation can be the alkyl carbon adjacent to N1. Such may be the case with ethano-adenine (EA), a DNA adduct formed by an important anticancer drug, BCNU...
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ژورنال
عنوان ژورنال: Biochemical Journal
سال: 2017
ISSN: 0264-6021,1470-8728
DOI: 10.1042/bcj20161008