title: Chromosomal model for analysis of a long CTG/CAG tract stability in wild-type Escherichia coli and its nucleotide excision repair mutants.
abstract: Many human hereditary neurological diseases, including fragile X syndrome, myotonic dystrophy, and Friedreich's ataxia, are associated with expansions of the triplet repeat sequences (TRS) (CGG/CCG, CTG/CAG, and GAA/TTC) within or near specific genes. Mechanisms that mediate mutations of TRS include DNA replication, repair, and gene conversion and (or) recombination. The involvement of the repair systems in TRS instability was investigated in Escherichia coli on plasmid models, and the results showed that the deficiency of some nucleotide excision repair (NER) functions dramatically affects the stability of long CTG inserts. In such models in which there are tens or hundreds of plasmid molecules in each bacterial cell, repetitive sequences may interact between themselves and according to a recombination hypothesis, which may lead to expansions and deletions within such repeated tracts. Since one cannot control interaction between plasmids, it is also sometimes difficult to give precise interpretation of the results. Therefore, using modified lambda phage (lambdaInCh), we have constructed a chromosomal model to study the instability of trinucleotide repeat sequences in E. coli. We have shown that the stability of (CTG/CAG)68 tracts in the bacterial chromosome is influenced by mutations in NER genes in E. coli. The absence of the uvrC or uvrD gene products greatly enhances the instability of the TRS in the chromosome, whereas the lack of the functional UvrA or UvrB proteins causes substantial stabilization of (CTG/CAG) tracts.
authors: Department of Genetics of Microorganisms, University of Łódź, 90-237 Łódź, Banacha 12/16, Poland. pstaczek@biol.uni.lodz.pl
authors: Sylwia T
authors: ST
authors: Szwarocka
authors: Paweł
authors: P
authors: Staczek
authors: Paweł
authors: P
authors: Parniewski
mesh_terms: D002876:Chromosomes, Bacterial; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics*; D053842:Microsatellite Instability; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D018911:Trinucleotide Repeats