Rev1 and Polzeta influence toxicity and mutagenicity of Me-lex, a sequence selective N3-adenine methylating agent

DNA Repair
Paola MontiGilberto Fronza

Abstract

The relative toxicity and mutagenicity of Me-lex, which selectively generates 3-methyladenine (3-MeA), is dependent on the nature of the DNA repair background. Base excision repair (BER)-defective S. cerevisiae strains mag1 and apn1apn2 were both significantly more sensitive to Me-lex toxicity, but only the latter is significantly more prone to Me-lex-induced mutagenesis. To examine the contribution of translesion synthesis (TLS) DNA polymerases in the bypass of Me-lex-induced lesions, the REV3 and REV1 genes were independently deleted in the parental yeast strain and in different DNA repair-deficient derivatives: the nucleotide excision repair (NER)-deficient rad14, and the BER-deficient mag1 or apn1apn2 strains. The strains contained an integrated ADE2 reporter gene under control of the transcription factor p53. A centromeric yeast expression vector containing the wild-type p53 cDNA was treated in vitro with increasing concentrations of Me-lex and transformed into the different yeast strains. The toxicity of Me-lex-induced lesions was evaluated based on the plasmid transformation efficiency compared to the untreated vector, while Me-lex mutagenicity was assessed using the p53 reporter assay. In the present study, we demonstra...Continue Reading

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Citations

Nov 12, 2013·Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis·Paola MontiGilberto Fronza
Dec 14, 2012·Chemical Research in Toxicology·Prema IyerBarry Gold
Jan 13, 2012·Nature Reviews. Cancer·Dragony FuLeona D Samson
Oct 26, 2011·Molecular and Cellular Biology·Hugo WurteleAlain Verreault
Oct 12, 2010·Journal of Nucleic Acids·Samuel SettlesBarry Gold
Oct 31, 2009·Mutation Research·Paola MontiGilberto Fronza
Mar 5, 2015·DNA Repair·Alena V Makarova, Peter M Burgers
Sep 30, 2016·Nucleic Acids Research·Rajendra PrasadSamuel H Wilson

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