The "A" rule revisited: polymerases as determinants of mutational specificity.
Organisms control the specificity and frequency with which they mutate via their complement of proteins. The mismatch repair (MMR) proteins correct errors after they are made. The DNA polymerases of the cell determine the response to damaged DNA which has not been repaired by excision. Polymerase action can be considered as consisting of three main steps: addition of a base, proofreading of the added nucleotide and elongation. Each of these steps is kinetically complex and can be modulated. The modulation accounts for different behaviors of organisms in response to stress. The recent findings of DNA polymerases with properties appropriate for dealing with damaged DNA may help to account for the phenomenon of spontaneous mutation and for the hypermutability associated with immunoglobulin maturation and carcinogenesis.
Strauss
Bernard S
BS
Department of Molecular Genetics and Cell Biology, The University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA. bs19@midway.uchicago.edu
D000818:Animals; D020137:Base Pair Mismatch; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D006801:Humans; D016296:Mutagenesis; D009154:Mutation
D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase