title: Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage.
abstract: Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.
authors.affiliation: Laboratório de Radiobiologia Molecular, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Brazil.
authors.forename: Deise Fonseca
authors.initials: DF
authors.lastname: Felício
authors.forename: Leonardo da Silva
authors.initials: Lda S
authors.lastname: Vidal
authors.forename: Roberto Silva
authors.initials: RS
authors.lastname: Irineu
authors.forename: Alvaro Costa
authors.initials: AC
authors.lastname: Leitão
authors.forename: Wanda Almeida
authors.initials: WA
authors.lastname: von Kruger
authors.forename: Constança de Paoli
authors.initials: Cde P
authors.lastname: Britto
authors.forename: Angélica
authors.initials: A
authors.lastname: Cardoso
authors.forename: Janine Simas
authors.initials: JS
authors.lastname: Cardoso
authors.forename: Claudia
authors.initials: C
authors.lastname: Lage
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D053904:DNA Breaks, Single-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D011401:Promoter Regions, Genetic; D013014:SOS Response, Genetics / Q000235:genetics*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C058093:UvrB protein, E coli; D004706:Endodeoxyribonucleases; C066567:UvrC protein, E coli; C448636:Cho protein, E coli; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D002945:Cisplatin