The biochemical basis of 5-bromouracil- and 2-aminopurine-induced mutagenesis.
We describe in vitro measurements of heteroduplex base mispaired intermediates involving 5-bromouracil and 2-aminopurine in A X T----G X C and G X C----A X T transition mutation pathways. For the case of 2-aminopurine, 2-aminopurine X cytosine mispairs are formed at a much higher frequency than adenine X cytosine mispairs in either transition pathway. For the case of 5-bromouracil, at least a 40-fold increase in 5-bromouracil X guanine mispairs are observed over thymine X guanine mispairs but only in the G X C----A X T pathway. In the A X T----G X C pathway, mispairs involving 5-bromouracil are formed 2.5-fold more frequently to those involving thymine suggesting perhaps that 5-bromouracil may exhibit substantially different base-pairing behavior depending on whether it is present as a template base or as a deoxyribonucleosides triphosphate substrate. The effect of the base analogs on dNTP pool size perturbations is discussed. A measurement of dNTP pools in 2-aminopurine mutagenized bacteriophage T4-infected cells is presented. An approximate eight-fold expansion in common dNTP pools is observed in a ts L141 antimutator genetic background compared to wild type T4 43+ and ts L56 mutator backgrounds. The effects of distorted dNTP pools on mutagenesis will be considered.
D015075:2-Aminopurine / Q000378:metabolism / Q000494:pharmacology*; D000225:Adenine / Q000031:analogs & derivatives*; D001482:Base Composition / Q000187:drug effects; D001976:Bromouracil / Q000378:metabolism / Q000494:pharmacology*; D003596:Cytosine / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D013941:Thymine / Q000378:metabolism
D003845:Deoxycytosine Nucleotides; D003854:Deoxyribonucleotides; D003856:Deoxyuracil Nucleotides; D009692:Nucleic Acid Heteroduplexes; C032549:bromodeoxyuridine triphosphate; C024107:2'-deoxycytidine 5'-triphosphate; D015075:2-Aminopurine; D001976:Bromouracil; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine