Replication and Mutagenesis of Irradiated Single-Strand Phage DNA
Mutagens may be divided into two classes on the basis of the mechanism of their mutagenic action and the requirement for cellular repair genes for their mutagenic effect. Direct mutagens cause subtle modifications of the bases in DNA (or its precursors) and give rise to mutations by mispairing during DNA replication. Direct mutagens do not require cellular DNA repair activity for their mutagenic effect (i.e. act independently of the bacterial recA and lexA genes) and normally have a high degree of mutagenic specificity, reflecting the specificity of mispairing. Examples of direct mutagens are deaminating agents, such as hydroxylamine and bisulfite ; some base analogs, such as 2-aminopurine ; and alkylating agents, such as ethylmethane sulfonate. Indirect mutagens destroy the coding properties of DNA templates, thereby blocking DNA replication, and, unless repaired, are lethal. In situations where there is a redundancy in the DNA sequence information error-free repair processes may eliminate (e.g. by excision repair) or ‘tolerate’ (e.g. by postreplication recombinational exchanges) these lesions. However, when the mutagen destroys a unique piece of DNA sequence information, repair by error-free processes is no longer possible, and recA lexA-dependent error-prone repair is the only alternative to lethality. Such a situation may occur when a non-coding lesion is located within an overlapping excision gap (1), or in an overlapping gap in nascent DNA (2), or in a single-stranded genome (3). Examples of indirect mutagens are ultraviolet (UV) and ionizing radiation and many chemical mutagens and carcinogens, such as aflatoxin B1, benzo(a)pyrene, and mitomycin C.
KeywordsPyrimidine Dimer Cold Spring Harbor Symposium Apurinic Site Dime Site Indirect Mutagen
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