Mutagenesis by incorporation of alkylated nucleotides.
The cellular DNA precursor pool was shown to be a target for N-methyl-N-nitrosourea, a potent mutagen and carcinogen. O6medGTP, a product of this interaction, was chemically synthesized and shown to be incorporated into DNA in vitro by Klenow E. coli pol I and phage T4 DNA polymerases. O6medGTP incorporated predominantly opposite T template residues and to a lower extent opposite C. At some loci incorporation of O6medGTP caused DNA synthesis arrest. The significance of the behavior of O6medGTP for mutagenesis in vivo is discussed.
D000478:Alkylation; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D008745:Methylation; D008770:Methylnitrosourea / Q000494:pharmacology; D009154:Mutation; D009694:Nucleic Acid Precursors / Q000378:metabolism*; D013698:Templates, Genetic
D003845:Deoxycytosine Nucleotides; D003848:Deoxyguanine Nucleotides; D003854:Deoxyribonucleotides; D009694:Nucleic Acid Precursors; C023827:O(6)-methyldeoxyguanosine triphosphate; D008770:Methylnitrosourea; C021203:N(4)-hydroxydeoxycytidine triphosphate; D004247:DNA; D004259:DNA-Directed DNA Polymerase