Two distinct models account for short and long deletions within sequence repeats in Escherichia coli

Abstract

In Escherichia coli, (GpC) n sequences cloned into plasmid DNA molecules are deletion-prone with the occurrence of both short (<2 bp) and long (>2 bp) deletion events. These repetitive tracts can be stabilized by interrupting the strict monotony of the repetition with a variant dinucleotide sequence. The stabilization of short deletion events that is mediated by the variant sequence is completely lost in E. coli mismatch repairdeficient strains. In contrast, this repair pathway has no influence on the frequency of occurrence of long deletion events, even in sequences containing the variant repeat. These results lead us to propose two distinct models to account for short and long deletions within repetitive sequences in E. coli. Furthermore, this study reveals that the deletions occur preferentially at the end of the repeat sequence that is distal with respect to the origin of replication.

Mutations in Haemophilus influenzae Mismatch Repair Genes Increase Mutation Rates of Dinucleotide Repeat Tracts but Not Dinucleotide Repeat-Driven Pilin Phase Variation Rates

“…Dinucleotide repeat tracts are destabilized by inactivation of any of the nonredundant major components of the E. coli MMR system (24,31). Previously, using a chromosomally located mod-AT20R-lacZ reporter gene, we showed that inactivation of H. influenzae mutS destabilized a tract of 20 5Ј AT dinucleotide repeats (5).…”

“…Comparisons of the spectra of spontaneous mutations for wild-type strains and MMR mutants reveal that MMR is active on all types of base substitutions and frameshifts, with the latter occurring most frequently in short tracts of the same base pair (23,30). Long DNA repeat tracts, termed microsatellites, with unit sizes of 1 or 2 nucleotides are highly unstable in E. coli MMR mutants (24,31,33), while the mutation rates of tetranucleotide repeat tracts are unaltered (10).…”

Identification of polymorphic tandem repeats by direct comparison of genome sequence from different bacterial strains : a web-based resource

“…It is also reminiscent of the behavior of microsatellites (also called short sequence repeats: SSR, see [45] for review), which are stabilized by internal variations [46] and by reduction of the number of repeats [47]. Unfortunately, we show here that such simple prediction criteria may miss a very large proportion of polymorphic tandem repeats, and provide highly variable results in different species.…”

Roles of Double-strand Breaks, Nicks, and Gaps in Stimulating Deletions of CTG·CAG Repeats by Intramolecular DNA Repair

“…For example, mis-pairs or small loop structures in repetitive DNA will be excised by mismatch repair or nucleotide excision repair proteins leading to DNA gaps. 21,[39][40][41][42][43][44][45][46][47][48] If these gaps are sufficiently long, secondary structures such as hairpins may be formed in the single-stranded repeat regions. Most models for deletions propose that during polymerization to fill in the gaps, the DNA polymerase will bypass the template hairpin structure.…”

“…[1][2][3][4][5] Several cellular factors have been shown to influence repeat stability including transcription, [20][21][22][23] DNA polymerase proofreading, [24][25][26] and DNA methylation. [27][28][29][30] Nevertheless, the three main DNA metabolic pathways (DNA replication, [31][32][33][34][35] recombination, [36][37][38] and repair 21,[39][40][41][42][43][44][45][46][47][48] have the strongest impact on genetic instabilities.…”