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Abstract
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.