Abstract
Azidothymidine (AZT) has been widely used since 1987 [21] to combat HIV I AIDS. AZT is thought to stop replication of viral DNA by getting incorporated into the DNA sequence and acting as a chain terminator. We constructed 15 strains of lacZ in wild-type and mutS backgrounds that contain specific point mutations, frameshift mutations or template switch mutation that can be restored to laczt by respectively correcting these mutations in only one way. Our studies investigate the effect of AZT on the reversion rates of these mutants by continuously exposing them to very doses low of AZT. For mutants carrying point mutation, it is still unclear how AZT affects their reversion due to insufficient data and technical difficulties while conducting the experiment. Mutants carrying frameshift mutation arc all equally affected by AZT by about 3 to 5 fold increase. mutS increases spontaneous reversion rates for frameshift mutants. However, mutS appears to have no repair effect on the damages caused by AZT. AZT shows the strongest effects on reversion rates of mutants requiring template switching to revert to wild-type. Two types of template switching involve in this study arc imperfect hairpins and sequence duplication. For mutants carrying hairpins, AZT dramatically the formation of perfect hairpins by template switch and for sequence duplicate mutant, AZT increases the rates by about 5-8 folds. mutS also exhibits little or no effect on the AZT damage in the sequence duplicates. However, it is unclear how and why AZT affects and favors template repeats mutants.