4-quinolones and the SOS response.
The SOS DNA repair system is induced in bacteria treated with 4-quinolones. However, whether the response exacerbates or repairs the damage caused by these drugs is still unclear. The recA13 and the recB21 mutations impair recombination repair and render bacteria unable to induce the SOS response when treated with nalidixic acid or other agents that affect DNA synthesis. However, UV treatment induces the SOS response in recB21 mutants but not in recA13 mutants. Both these mutants are hypersensitive to nalidixic acid and, therefore, either recombination repair or SOS repair would appear to repair DNA damage caused by the drug. However, since the lexA3 mutation (which also renders bacteria incapable of inducing the SOS response without affecting recombination repair) had no effect on the susceptibility of bacteria to nalidixic acid, the SOS response neither contributes to nor repairs DNA damage caused by the drug. Consequently, it would seem that the hypersensitivity of the recA13 and recB21 mutants to nalidixic acid is due to their deficiency in recombination repair. This view was confirmed by testing a recA430 mutant that is recombination-repair proficient but SOS repair-deficient and finding it to be no more sensitive to nalidixic acid than its parent. Thus it would appear that, although induced by nalidixic acid treatment, the SOS DNA repair system does not play any role in bacterial responses to the damage caused by the drug. In contrast, the recombination repair system does repair damage caused by nalidixic acid.
Lewin
C S
CS
Department of Pharmaceutics, School of Pharmacy, London University, Brunswick Square.
Howard
B M
BM
Ratcliffe
N T
NT
Smith
J T
JT
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000235:genetics; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology*; D011938:Rec A Recombinases / Q000235:genetics; D011995:Recombination, Genetic; D013014:SOS Response, Genetics / Q000187:drug effects; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases; D009268:Nalidixic Acid; D011938:Rec A Recombinases; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein