The Biochemistry of Mutagenesis

Mutagenesis has remained an intriguing aspect of genetics since the beginning of this century, and its analysis has proceeded hand in hand with the elucidation of gene replication and expression. Interest in this area has further heightened with the growing awareness that numerous environmental agents may cause mutations in humans. These mutations may lead to metabolic as well as neoplastic diseases. Advances during the past 15 years have revealed two major classes of mutagenic mechanisms: directly induced base mispairing, and misrepair. Alkylating agents for instance, generate many different reaction products in DNA, but only two of these (O6-alkylguanine and O4-alkylthymine) are likely candidates for directly induced mispairing. He has also turned out to be an important mutagen, one that presents a particular serious challenge to large genomes; it converts cytosine to uracil and guanine to an analogue of cytosine. DNA lesions that interrupt DNA chain elongation, including many of other products of alkylation, often trigger an error-prone postreplication repair process. Current evidence suggests that this process involves in incorrect insertion of bases into gaps in progeny-strand DNA opposite such a lesion. Mutagenic mechanisms are subject to powerful genetic controls that include the activities of DNA polymerases in the selection of deoxynucleoside triphosphates and the removal of incorrectly inserted nucleotides.