title: Mutation in Escherichia coli under starvation conditions: a new pathway leading to small deletions in strains defective in mismatch correction.
abstract: Strains of Escherichia coli carrying the mutY mutation lack a mismatch correction glycosylase that removes adenines from various mismatch situations. In growing bacteria, 8-oxoguanine-adenine mispairs persist and can give rise to G-->T transversions during subsequent replication cycles. We now show that when trpA23 mutY bacteria are held under tryptophan starvation conditions the tryptophan-independent mutants that arise include small in-frame deletions in addition to transversions. The trpA23 reversion system appears to be unusual in that small in-frame deletions occurring in a particular region of the gene can lead to the production of a functional protein. We suggest that this is a consequence of the deletion causing the polar group on the arginine at the trpA23 site to be pulled away from the active site of the enzyme. Such deletions are also found with starved bacteria defective in methyl-directed mismatch correction activity (mutH, mutL or mutS), and deletion mutations are also found among the much lower number of mutants that arise in bacteria wild-type for mismatch correction. There is thus a pathway, hitherto undetected, leading to deletions probably from mismatches under conditions of growth restraint. RecA, UmuC, UvrA, MutH,L,S, SbcC and SbcD proteins are not required for the operation of the deletion pathway. A possible explanation is that the deletion pathway is not dependent upon further replication and that it fails to be discernible in growing cells because it is relatively slow acting and mismatches are likely to encounter a DNA replication fork before the initial step of the deletion pathway.
authors.affiliation: Medical Research Council Cell Mutation Unit, University of Sussex, Falmer, Brighton, UK. b.a.bridges@sussex.ac.uk
authors.forename: B A
authors.initials: BA
authors.lastname: Bridges
authors.forename: A R
authors.initials: AR
authors.lastname: Timms
mesh_terms: D001483:Base Sequence; D045647:DNA Glycosylases; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D016364:Reading Frames; D017384:Sequence Deletion; D014364:Tryptophan / Q000172:deficiency; D014367:Tryptophan Synthase / Q000235:genetics
chemical_list: D014364:Tryptophan; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D014367:Tryptophan Synthase