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      The “A” rule revisited: polymerases as determinants of mutational specificity

      DNA Repair
      Elsevier BV

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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.

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          Author and article information

          Journal
          DNA Repair
          DNA Repair
          Elsevier BV
          15687864
          February 2002
          February 2002
          : 1
          : 2
          : 125-135
          Article
          10.1016/S1568-7864(01)00014-3
          12509259
          fb874b8b-d7ac-44ac-bae3-cc386221b177
          © 2002

          http://www.elsevier.com/tdm/userlicense/1.0/

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