Toxicity and tolerance mechanisms for azidothymidine, a replication gap-promoting agent, in Escherichia coli.

ABSTRACT: Azidothymidine (AZT, zidovudine) is used to treat HIV-AIDS and prevent maternal transmission to newborns. Because the azido group replaces the 3' OH of thymidine, AZT is believed to act as a chain terminator during reverse transcription of viral RNA into DNA, although other mechanisms of viral inhibition have been suggested. There is evidence that AZT is genotoxic, particularly to the mitochondria. In this study, we use the bacterium Escherichia coli to investigate the mechanism of AZT toxicity and the cellular mechanisms that aid survival. We show that that replication arrests quickly after treatment, accompanied by induction of the SOS DNA damage response. AZT appears to produce single-strand DNA gaps, as evident by RecF-dependent induction of the SOS response and visualization of single

SUBMITTER: Cooper DL 

PROVIDER: S-EPMC3046245 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature