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, rep...

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Bibliographic Details
Published in:Chemical research in toxicology 2006-10, Vol.19 (10), p.1351-1356
Main Authors: Vidal, Leonardo S, Santos, Larissa B, Lage, Claudia, Leitão, Alvaro C
Format: Article
Language:English
Subjects:
Cell Survival - drug effects
Cell Survival - radiation effects
DNA Adducts - genetics
DNA Helicases - genetics
DNA Repair - drug effects
DNA Repair - genetics
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli - radiation effects
Escherichia coli Proteins - genetics
Mitomycin - pharmacology
Mutation - genetics
Rec A Recombinases - genetics
Rec A Recombinases - metabolism
Sensitivity and Specificity
Ultraviolet Rays
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Summary: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.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx060035y