title: Roles of recA mutant allele (recA495) in frameshift mutagenesis.
abstract: The chemical carcinogen N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) induces frameshift mutations located within two types of specific sequences (mutation hot spots): i) contiguous guanine sequences and ii) alternating GC sequences. The genetic requirements of these frameshift events were investigated using specific reversion assays. AAF-induced -2 frameshift mutagenesis at alternating GC sequences is peculiar in that it requires a LexA- controlled function which is not UmuDC and occurs in the absence of RecA protein, provided the SOS regulon is derepressed. Moreover, the non-activated form of the RecA protein was shown to act as an inhibitor in this mutation pathway. As we were interested in elucidating this mutation pathway, we have developed a convenient spot reversion assay specific for the detection of this class of mutations. This assay allowed us to isolate E coli mutants affected either in repair or mutagenesis functions. One particular mutant, recA495, is very sensitive to UV and N-AcO-AAF, and is defective in recombination and UV mutagenesis. The RecA495 protein exhibits very low binding to both single- and double-stranded DNA. We show that when the SOS regulon is derepressed, the recA495 allele has two contrasting roles in frameshift mutagenesis: i) it prevents the induction of -1 frameshift mutations at repetitive sequences and ii) it is permissive for the induction of -2 frameshift mutations within alternating GC sequences.
authors.affiliation: Groupe de Cancérogenèse et de Mutagenèse Moléculaire et Structurale, Institut de Biologie Moléculaire et Cellulaire du CNRS (IBMC), Strasbourg, France.
authors.forename: R
authors.initials: R
authors.lastname: Janel-Bintz
authors.forename: G
authors.initials: G
authors.lastname: Maenhaut-Michel
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: R P
authors.initials: RP
authors.lastname: Fuchs
mesh_terms: D000483:Alleles; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics*; D016368:Frameshift Mutation; D005798:Genes, Bacterial; D016296:Mutagenesis; D011938:Rec A Recombinases / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D011938:Rec A Recombinases