Mutagenesis lesion-induced

Induced mutagenesis in Escherichia coli is an active process involving proteins with DNA replication, repair, and recombination functions. The available evidence suggests that mutations are generated at sites where DNA has been damaged and that they arise via an error-prone repair activity. In an attempt to understand what specific contributions to mutagenesis are made by DNA lesions, we have studied the mutational specificity of some carcinogens, such as benzo[a]pyrene and aflatoxin, whose chemical reactions with DNA are... 

The well characterized reactions of carcinogens such as benzols] pyrene and aflatoxin B with DNA (39-50) suggested to us that an analysis of the kinds of mutations these agents induced could shed light on the contribution of specific DNA lesions to mutagenesis. 

Vogel, E.W. (1989) Somatic cell mutagenesis in Drosophila, recovery of genetic damage in relation to the types of DNA lesions induced in mutationally unstable and stable X-chromo-somes. Mutat. Res.. 211. 153-170... 

Error-free versus error-prone is a relative description for the accuracy of translesion synthesis. Sometimes, it may not be obvious to distinguish between error-free and error-prone based on in vitro biochemical analysis of a polymerase in response to a specific lesion. The ultimate distinction between these two modes of translesion synthesis in cells can be made through genetic analysis. If the polymerase activity suppresses the lesion-induced mutagenesis, then, it is error-free. If the polymerase activity promotes the lesion-induced mutagenesis, then, it is error-prone. 

Surprisingly, human Poll prefers A incorporation opposite the 3 T of a template TT (6-4) photoproduct, in contrast to the much preferred G incorporation opposite the undamaged template T. Nucleotide incorporation opposite the 5 T of the TT (6-4) photoproduct, however, is largely blocked by the lesion. Opposite a template TT dimer, human Poll has a very limited activity, preferentially incorporating a T opposite the 3 T of the lesion. This activity, albeit very inefficient, may contribute to TT dimer-induced mutagenesis in XPV cells that lack Polr. ... 

Nakano, T., Asagoshi, K., Terato, H., Suzuki, T., and Ide, H. (2005) Assessment of the genotoxic potential of nitric oxide-induced guanine lesions by in vitro reactions with Escherichia coli DNA polymerase I. Mutagenesis, 20, 209-216. 

---