Genetic control of AAF-induced mutagenesis at alternating GC sequences: an additional role for RecA.
In a previous study, the forward mutation spectrum induced by the chemical carcinogen N-acetoxy-N-2-acetylaminofluorene was determined (Koffel-Schwartz et al. 1984). It was found that 90% of the induced mutations are frameshift mutations located within specific sequences (mutation hot spots). Two classes of mutation hot spots were found: (i) -1 frameshift mutations occurring within runs of guanines (i.e. GGGG----GGG; (ii) -2 frameshift mutations occurring within the NarI recognition sequence (GGCGCC----GGCC). In the present work, we further investigate the genetic requirements of these frameshift events by using specific reversion assays. Like UV-induced mutagenesis, frameshift mutations occurring within runs of G's (also referred to as the "slippage pathway") require the activated form of the RecA protein (RecA*). On the other hand, frameshift mutations occurring at the NarI site (the "NarI mutation pathway") require a LexA-controlled function(s) that is not UmuDC. The LexA-controlled gene(s) that is (are) involved in this pathway remain to be identified. Moreover, this pathway does not require RecA* for the proteolytic processing of a protein other than LexA (like the cleavage of UmuD in UV-induced mutagenesis). An "additional" role of RecA can be defined as follows: (i) The non-activated form of the RecA protein acts as an inhibitor in the NarI mutation pathway. (ii) This inhibition is relieved upon activation of RecA by UV irradiation of the bacteria. (iii) A recA deletion mutant is totally proficient in the NarI mutation pathway provided the SOS system is derepressed [lexA (Def) allele]. Therefore, RecA does not actively participate in the fixation of the mutation. A molecular model for this "additional" role of RecA is proposed.
Koffel-Schwartz
N
N
Institut de biologie moléculaire et cellulaire du CNRS, Strasbourg, France.
Fuchs
R P
RP
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology*; D001483:Base Sequence; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D005798:Genes, Bacterial; D005838:Genotype; D009154:Mutation; D010641:Phenotype; D010957:Plasmids; D011938:Rec A Recombinases / Q000502:physiology*
D000099:Acetoxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D011938:Rec A Recombinases