We used the lacI system of Escherichia coli to examine the distribution of -base substitution mutations occurring spontaneously in different mismatch-repair-deficient strains. The examination of almost 1,200 nonsense mutations generated in strains carrying the mutS, mutH, and mutU alleles confirmed that transitions are highly favored over transversions. The detailed analysis of relative mutation rates at different sites revealed that the pattern of hot spots and cold spots is strikingly similar in each of the three strain backgrounds, strongly supporting the notions that the products of the three genes are part of the same system and that in the absence of any of the components the entire system fails to function. The distribution of mutations occurring in the absence of mismatch repair defined a pronounced topography of the lacI gene. There was no obvious correlation of the hot spots or cold spots with either nearest-neighbor sequences or A T richness of the immediate surrounding sequence.

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