Preparation and template activities of polynucleotides containing O2- and O4-alkyluridine.
O2-Ethyl-UDP and O4-methyl-UDP have been prepared and copolymerized in various proportions with UDP or CDP, using polynucleotide phosphorylase. The copolymers were used as templates for DNA-dependent RNA polymerases in the presence of Mn2+. Both of the O-alkylated uridines caused a similar misincorporations. When copolymerized with U they led to incorporation of CMP and GMP into the poly(A). No AMP or UMP incorporation seemed to be caused by the introduction of O-alkyluridines into either poly(U) or poly(C). The mispairing of O2- and O4-alkyluridine to behave like C or G represents mutagenic events. O2 alkylation of U or T is, in contrast to O4 alkylation, a relatively frequent result of treatment of double-stranded nucleic acids with N-nitroso alkylating agents. In single-stranded nucleic acids both O2 and O4 alkylations of U and T occur to similar extents. Thus, the observed mutagenic effects of O2 and O4 alkylation of U may be involved in the high carcinogenicity of these alkylating agents.
D000478:Alkylation; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D009154:Mutation; D011131:Polyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D013329:Structure-Activity Relationship; D013698:Templates, Genetic; D014529:Uridine / Q000031:analogs & derivatives*
D011131:Polyribonucleotides; D012321:DNA-Directed RNA Polymerases; D014529:Uridine
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