Rm. Schaaper, BASE SELECTION, PROOFREADING, AND MISMATCH REPAIR DURING DNA-REPLICATION IN ESCHERICHIA-COLI, The Journal of biological chemistry, 268(32), 1993, pp. 23762-23765
The accuracy by which organisms duplicate their DNA is of considerable
interest. At least three mechanisms operate, serially, to secure high
fidelity: base selection, exonucleolytic proofreading, and postreplic
ative mismatch correction. To obtain insights into the efficiency and
specificity of these steps in the bacterium Escherichia coli, we have
performed DNA sequence analysis of mutations occurring in the bacteria
l lacI gene in a series of strains genetically disabled in one or more
of these error avoidance pathways. The base selection efficiency was
estimated from mutagenesis occurring in a mutDmutL strain, which is de
ficient in both proofreading (mutD5) and mismatch repair (mutL). The p
roofreading efficiency was derived comparing the mutD5 mutL strain to
the mismatch repair-deficient mutL strain. The efficiency of mismatch
repair was derived comparing the mutL strain to the wild-type strain.
The results show that base selection discriminates against errors by 2
00,000-2,000,000-fold, proofreading by 40-200-fold, and mismatch repai
r by 20-400-fold, each depending on the type of error. Base selection
and proofreading act more strongly against transversions than transiti
ons, whereas mismatch repair does the opposite. The data are based on
866 sequenced lacI mutations in a target that allows the scoring of at
least 127 different mutations in 76 distinct DNA sequence contexts in
vivo. They may therefore have general significance.