Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease
| Autor: | Gina Chun, Steven R. Patierno, Travis J. O’Brien, Kaveh Kahen, H. George Mandel, GuoHui Jiang, Craig S. Westphal, Akbar Montaser, J. Christopher States |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Chromium
DNA Repair DNA repair DNA damage Health Toxicology and Mutagenesis Bacillus Endonuclease chemistry.chemical_compound DNA Adducts Plasmid Chromium Compounds Genetics Nucleotide UvrABC endonuclease chemistry.chemical_classification Endodeoxyribonucleases biology Escherichia coli Proteins Molecular biology chemistry Biochemistry biology.protein DNA Nucleotide excision repair DNA Damage Plasmids |
| Zdroj: | Mutation research. 610(1-2) |
| ISSN: | 0027-5107 |
| Popis: | Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect