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·T → G·C and G·C → A·T transition mutation pathways. For the case of 2-amino- purine, 2-aminopurine·cytosine mispairs are formed at a much higher frequency than adenine·cytosine mispairs in either transition pathway. For the case of 5-bromouracil, at least a 40-fold increase in 5-bromouracil-guanine mispairs are observed over thymine·guanine mispairs but only in the A·T → G·C pathway. In the A·T → G·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.
KeywordsBiochemical Basis Template Strand Base Analog dNTP Pool Prime Strand
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