Molecular Structure of Binary Chromium(III)–DNA Adducts

Chromium(VI) is a carcinogen and mutagen, and its mechanisms of action are proposed to involve binding of its reduction product, chromium(III), to DNA. The manner in which chromium(III) binds DNA has not been established, particularly at a molecular level. Analysis of oligonucleotide duplex DNAs by...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2020-03, Vol.21 (5), p.628-631
Main Authors: Brown, Silas, Lockart, Molly M., Thomas, C. Sumner, Bowman, Michael K., Woski, Stephen A., Vincent, John B.
Format: Article
Language:English
Subjects:
Adducts
Binding Sites
Carcinogens
Chromium
Chromium - chemistry
Crosslinking
Deoxyribonucleic acid
DNA
DNA adducts
DNA Adducts - chemistry
ESEEM
Guanine
Guanine - chemistry
Molecular Structure
NMR
Nuclear magnetic resonance
Oligonucleotides
Oligonucleotides - chemistry
Oxidation-Reduction
paramagnetic NMR spectroscopy
Phosphates
Trivalent chromium
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Summary:Chromium(VI) is a carcinogen and mutagen, and its mechanisms of action are proposed to involve binding of its reduction product, chromium(III), to DNA. The manner in which chromium(III) binds DNA has not been established, particularly at a molecular level. Analysis of oligonucleotide duplex DNAs by NMR, EPR, and IR spectroscopies in the presence of chromium(III) allows the elucidation of the Cr binding site. The metal centers were found to interact exclusively with guanine N7 positions. No evidence of chromium interactions with other bases or backbone phosphates nor of Cr forming intra‐strand crosslinks between neighboring guanine residues was observed. No (back)bones about it: A combination of NMR, EPR, and FTIR spectroscopic studies demonstrate that chromium(III), the ultimate reduction product of the carcinogen chromate, forms binary adducts at the N7 atom of guanine with no binding to the phosphate backbone.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201900436