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Deoxyribonuclease I footprinting reveals different DNA binding modes of bifunctional platinum complexes
Author(s) -
Chválová Kateřina,
Kašpárková Jana,
Farrell Nicholas,
Brabec Viktor
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05356.x
Subject(s) - footprinting , bifunctional , deoxyribonuclease , dna , deoxyribonuclease i , platinum , dna footprinting , chemistry , microbiology and biotechnology , biochemistry , biophysics , dna binding protein , biology , transcription factor , gene , base sequence , catalysis
Deoxyribonuclease I (DNase I) footprinting methodology was used to analyze oligodeoxyribonucleotide duplexes containing unique and single, site‐specific adducts of trinuclear bifunctional platinum compound, [{ trans ‐PtCl(NH 3 ) 2 } 2 μ‐ trans ‐Pt(NH 3 ) 2 {H 2 N(CH 2 ) 6 NH 2 } 2 ] 4+ (BBR3464) and the results were compared with DNase I footprints of some adducts of conventional mononuclear cis ‐diamminedichloroplatinum(II) (cisplatin). These examinations took into account the fact that the local conformation of the DNA at the sites of the contacts of DNase I with DNA phosphates, such as the minor groove width and depth, sequence‐dependent flexibility and bendability of the double helix, are important determinants of sequence‐dependent binding to and cutting of DNA by DNase I. It was shown that various conformational perturbations induced by platinum binding in the major groove translated into the minor groove, allowing their detection by DNase I probing. The results also demonstrate the very high sensitivity of DNase I to DNA conformational alterations induced by platinum complexes so that the platinum adducts which induce specific local conformational alterations in DNA are differently recognized by DNase I.