The first proposal for a mechanism of mutation induction in molecular terms was possible when WATSON and CRICK in 1953 elucidated the structure of DNA. Basing on this structure the authors not only proposed a mechanism for the transfer of genetic information from a parent to its offspring, but also a mechanism of mutation induction. It was suggested that mutations arise when rare tautomeric forms of the nucleobases cause illegitimate pairing during the process of replication leading to base-pair substitutions. Other causes of base-pair substitutions were soon found in chemical alterations of DNA components. FREESE explained the mutagenic effect of base analogs and hydroxylamine in a “direct” mutagenesis model (FREESE, 1). According to this model, base-pair substitutions of the transition and transversion type can occur, when — as a consequence of chemical alterations — pairing of the complementary bases adenine-thymine and guanine-cytpsine is no longer possible (FREESE, 2). For example, instead of pairing with thymine, adenine now pairs with cytosine (transition) or guanine (transversion). Other types of mutations, i.e. frameshift mutations, were explained in this direct mutagenesis model by BRENNER et al. who found that additions or deletions of bases in the DNA can be caused by dyes, such as acridine orange and others by intercalation between nucleobases.
KeywordsAlkylating Agent Mutation Induction Chemical Alteration Pyrimidine Dimer Chemical Mutagenesis
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