Enhanced sensitivity of Escherichia coli uvrB mutants to mitomycin C points to a UV-C distinct repair for DNA adducts.
Nucleotide excision repair (NER) in Escherichia coli repairs DNA by incising the damaged strand on the 3' and 5' sides of the lesion within pyrimidine dimers and DNA cross-linking adducts. Cross-linking adducts belong to a class of chemical damage to DNA that prevent strand separation, and thus, replication and transcription. For this reason, cross-linking agents such as mitomycin C (MC) have been used in cancer chemotherapy. The mechanisms involved in MC binding to DNA have already been defined; however, the repair of these lesions is not fully understood. Our goal was to study the repair of MC DNA lesions in E. coli cells. Several bacterial strains with specific mutations were tested for cellular inactivation and kinetics of DNA repair through analysis of DNA sedimentation profiles in alkaline sucrose gradients. The results obtained show that uvrB mutants are extremely sensitive to MC in contrast to the other isogenic uvrA and uvrC mutant strains. uvrB mutant strains are unable to repair DNA strand breaks produced by MC. Thus, UvrB might play a NER-uncoupled role in the repair of lesions induced by MC in vivo, different from its role on the repair of lesions produced by UV-C. Also it is suggested that a modified NER system is taking place in the repair of MC-adducts.
Vidal
Leonardo S
LS
Lab. Radiobiologia Molecular, Inst. Biofísica Carlos Chagas Filho, CCS-UFRJ, 21949540, Rio de Janeiro, RJ, Brazil.
Santos
Larissa B
LB
Lage
Claudia
C
Leitão
Alvaro C
AC
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018736:DNA Adducts / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*; D029968:Escherichia coli Proteins / Q000235:genetics*; D016685:Mitomycin / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D014466:Ultraviolet Rays
D018736:DNA Adducts; D029968:Escherichia coli Proteins; C058093:UvrB protein, E coli; D016685:Mitomycin; D011938:Rec A Recombinases; D004265:DNA Helicases