title: Escherichia coli frameshift mutation rate depends on the chromosomal context but not on the GATC content near the mutation site.
abstract: Different studies have suggested that mutation rate varies at different positions in the genome. In this work we analyzed if the chromosomal context and/or the presence of GATC sites can affect the frameshift mutation rate in the Escherichia coli genome. We show that in a mismatch repair deficient background, a condition where the mutation rate reflects the fidelity of the DNA polymerization process, the frameshift mutation rate could vary up to four times among different chromosomal contexts. Furthermore, the mismatch repair efficiency could vary up to eight times when compared at different chromosomal locations, indicating that detection and/or repair of frameshift events also depends on the chromosomal context. Also, GATC sequences have been proved to be essential for the correct functioning of the E. coli mismatch repair system. Using bacteriophage heteroduplexes molecules it has been shown that GATC influence the mismatch repair efficiency in a distance- and number-dependent manner, being almost nonfunctional when GATC sequences are located at 1 kb or more from the mutation site. Interestingly, we found that in E. coli genomic DNA the mismatch repair system can efficiently function even if the nearest GATC sequence is located more than 2 kb away from the mutation site. The results presented in this work show that even though frameshift mutations can be efficiently generated and/or repaired anywhere in the genome, these processes can be modulated by the chromosomal context that surrounds the mutation site.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, República Argentina.
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Martina
authors.forename: Elisa M E
authors.initials: EM
authors.lastname: Correa
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Argaraña
authors.forename: José L
authors.initials: JL
authors.lastname: Barra
mesh_terms: D001483:Base Sequence; D002876:Chromosomes, Bacterial / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics* / Q000378:metabolism; D048168:Escherichia coli K12 / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics; D016368:Frameshift Mutation; D005798:Genes, Bacterial; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics; D059645:Mutation Rate; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D009692:Nucleic Acid Heteroduplexes; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli