Inducible repair of alkylated DNA in microorganisms

Mutation Research. Reviews in Mutation Research
Damian MieleckiElżbieta Grzesiuk

Abstract

Alkylating agents, which are widespread in the environment, also occur endogenously as primary and secondary metabolites. Such compounds have intrinsically extremely cytotoxic and frequently mutagenic effects, to which organisms have developed resistance by evolving multiple repair mechanisms to protect cellular DNA. One such defense against alkylation lesions is an inducible Adaptive (Ada) response. In Escherichia coli, the Ada response enhances cell resistance by the biosynthesis of four proteins: Ada, AlkA, AlkB, and AidB. The glycosidic bonds of the most cytotoxic lesion, N3-methyladenine (3meA), together with N3-methylguanine (3meG), O(2)-methylthymine (O(2)-meT), and O(2)-methylcytosine (O(2)-meC), are cleaved by AlkA DNA glycosylase. Lesions such as N1-methyladenine (1meA) and N3-methylcytosine (3meC) are removed from DNA and RNA by AlkB dioxygenase. Cytotoxic and mutagenic O(6)-methylguanine (O(6)meG) is repaired by Ada DNA methyltransferase, which transfers the methyl group onto its own cysteine residue from the methylated oxygen. We review (i) the individual Ada proteins Ada, AlkA, AlkB, AidB, and COG3826, with emphasis on the ubiquitous and versatile AlkB and its prokaryotic and eukaryotic homologs; (ii) the organiza...Continue Reading

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Citations

Dec 6, 2017·International Journal of Molecular Sciences·Riccardo MiggianoMaria Ciaramella
Oct 28, 2019·Nature Communications·Katy PoncinXavier De Bolle
Mar 12, 2020·Frontiers in Microbiology·Kristin GrøsvikSvein Bjelland
May 11, 2018·The Journal of Biological Chemistry·Steven G Clarke
Apr 15, 2017·The Biochemical Journal·Małgorzata DylewskaAgnieszka M Maciejewska
Sep 19, 2019·Aquatic Toxicology·Małgorzata GrzesiukElżbieta Grzesiuk
Mar 13, 2019·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Mark M MuenterPenny J Beuning
Oct 29, 2020·Chemical Research in Toxicology·Katelyn L Rioux, Sarah Delaney

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