Enhancement of binding rate of RecA protein to DNA by carcinogenic benzo[a]pyrene derivatives and selective change of adduct conformation.
The association kinetics of RecA protein from Escherichia coli to DNA is strongly enhanced if even a minor fraction of DNA bases has been modified by a carcinogenic (+)-anti metabolite of benzo[a]pyrene (BPDE). The enhancement is much smaller with the less carcinogenic (-)-anti enantiomer of BPDE suggesting the possibility that the RecA protein binds selectively to the proto-oncogenic target. Most importantly, the binding of RecA to DNA modified with the latter enantiomer is found to give rise to a reorganization of this BPDE adduct from an intercalation site into a minor groove site. This indicates that the binding mechanism of RecA is via intercalation of some amino acid moiety, a discovery that could explain the approximately 50% contour length increase of the DNA within its fibrous complex with RecA.
Kim
S K
SK
Department of Physical Chemistry, Chalmers University of Technology, Gothenburg, Sweden.
Takahashi
M
M
Jernström
B
B
Nordén
B
B
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D007700:Kinetics; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011938:Rec A Recombinases / Q000378:metabolism*; D013237:Stereoisomerism
D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D011938:Rec A Recombinases