Reference - Detail
|Author||Sutherland JH, Tse-Dinh YC.|
|Title||Analysis of RuvABC and RecG involvement in the escherichia coli response to the covalent topoisomerase-DNA complex.|
Topoisomerases form a covalent enzyme-DNA intermediate after initial DNA cleavage. Trapping of the cleavage complex formed by type IIA topoisomerases initiates the bactericidal action of fluoroquinolones. It should be possible also to identify novel antibacterial lead compounds that act with a similar mechanism on type IA bacterial topoisomerases. The cellular response and repair pathways for trapped topoisomerase complexes remain to be fully elucidated. The RuvAB and RecG proteins could play a role in the conversion of the initial protein-DNA complex to double-strand breaks and also in the resolution of the Holliday junction during homologous recombination. Escherichia coli strains with ruvA and recG mutations are found to have increased sensitivity to low levels of norfloxacin treatment, but the mutations had more pronounced effects on survival following the accumulation of covalent complexes formed by mutant topoisomerase I defective in DNA religation. Covalent topoisomerase I and DNA gyrase complexes are converted into double-strand breaks for SOS induction by the RecBCD pathway. SOS induction following topoisomerase I complex accumulation is significantly lower in the ruvA and recG mutants than in the wild-type background, suggesting that RuvAB and RecG may play a role in converting the initial single-strand DNA-protein cleavage complex into a double-strand break prior to repair by homologous recombination. The use of a ruvB mutant proficient in homologous recombination but not in replication fork reversal demonstrated that the replication fork reversal function of RuvAB is required for SOS induction by the covalent complex formed by topoisomerase I.
|MeSH||Anti-Bacterial Agents / pharmacology Bacterial Proteins / genetics Bacterial Proteins / metabolism Colony Count, Microbial DNA Gyrase / genetics DNA Gyrase / metabolism DNA Helicases* / genetics DNA Helicases* / metabolism DNA Repair DNA Topoisomerases, Type I / genetics DNA Topoisomerases, Type I / metabolism* DNA, Bacterial / genetics DNA, Bacterial / metabolism* Endodeoxyribonucleases / genetics Endodeoxyribonucleases / metabolism Escherichia coli* / drug effects Escherichia coli* / enzymology Escherichia coli* / genetics Escherichia coli* / growth & development Escherichia coli Proteins* / genetics Escherichia coli Proteins* / metabolism Microbial Sensitivity Tests Mutation Norfloxacin / pharmacology Recombination, Genetic SOS Response (Genetics)|
|Prokaryotes E. coli||JW1850-2(Keio) JW3627-1(Keio) JW1852-1(Keio)|