Open AccessPolymorphism in N-2-acetylaminoflurene induced Dna Struture as reveled by Dnase I footprinting
Author(s) -
Xaveir Veaute,
Robert Fuchs
Publication year - 1991
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/19.20.5603
Subject(s) - guanine , biology , dna , footprinting , frameshift mutation , adduct , microbiology and biotechnology , base pair , dna adduct , deoxyribonuclease i , mutagenesis , genetics , mutation , nucleotide , gene , base sequence , chemistry , organic chemistry
In this paper, we have constructed double stranded helices (60-mers) containing a single N-2-acetylaminofluorene (-AAF) adduct covalently bound to one of the three guanine residues of the Narl site (G1G2CG3CC). This sequence was identified as a strong frameshift mutation hot spot for many carcinogens that bind to the C8 position of guanine. Using DNase I as a probe for DNA conformation we show i) that the average size of the helix deformation extends over 3 to 5 base pairs in both directions from the adduct site, and ii) that there is a strong polymorphism in the adduct induced DNA conformation. The present study supports the idea that adducts induce specific sequence dependent local conformational changes in DNA that are differentially recognized and processed by the enzymatic machineries that lead to repair or mutagenesis.