Adaptive mutation sequences reproduced by mismatch repair deficiency.
Adaptive reversions of a lac frameshift mutation in Escherichia coli are -1 deletions in small mononucleotide repeats, whereas growth-dependent reversions are heterogeneous. The adaptive mutations resemble instability of simple repeats, which, in hereditary colon cancer, in yeast, and in E. coli occurs in the absence of mismatch repair. The postulate that mismatch repair is disabled transiently during adaptive mutation in E. coli is supported here by the demonstration that the growth-dependent mutation spectrum can be made indistinguishable from adaptive mutations by disallowing mismatch repair during growth. Physiologically induced mismatch repair deficiency could be an important mutagenic mechanism in cancers and in evolution.
Longerich
S
S
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Galloway
A M
AM
Harris
R S
RS
Wong
C
C
Rosenberg
S M
SM
D001426:Bacterial Proteins / Q000235:genetics; D001482:Base Composition; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D006801:Humans; D056968:Lac Repressors; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017384:Sequence Deletion; D014161:Transduction, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins; D001616:beta-Galactosidase