Deoxyribonucleotide pools, base pairing, and sequence configuration affecting bromodeoxyuridine- and 2-aminopurine-induced mutagenesis.
- 1 April 1980
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 77 (4), 1801-1805
- https://doi.org/10.1073/pnas.77.4.1801
Abstract
Despite recent experiments showing that BrdUrd[bromodeoxyuridine]-induced mutagenesis can be independent of the level of bromouracil (BrUra) substitution, BrUra .cntdot. G base mispairs are a major determinant of mutagenesis. The experiments cited above are sensitive predominantly to G .cntdot. C .fwdarw. A .cntdot. T transitions driven by the immeasurably small but highly mutagenic substitution of BrUra for cytosine and not by the gross substitution of BrUra for thymine in DNA. BrdUrd and 2-aminopurine have 2 mutagenic effects intracellularly: perturbation of normal deoxyribonucleoside triphosphate pools, and analog mispairs in DNA. A molecular basis was proposed for various observations of normal exogenous deoxyribonucleosides as synergists and counteragents to base analog mutagenesis. A model is proposed to explain the antipolarity of BrdUrd and 2-aminopurine mutagenesis, i.e., why mutants at hot spots for induction by 1 base analog are usually hot spots for reversion by the other. The configuration of the neighboring nucleotides surrounding the base analog mispair, and not the base analogue''s preference for inducing A .cntdot. T .fwdarw. G .cntdot. C .fwdarw. A .cntdot. T errors, is responsible for the antipolarity of BrdUrd and 2-aminopurine mutagenesis.This publication has 64 references indexed in Scilit:
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