TY - JOUR
T1 - Binding of Sp1 to the 21-bp repeat region of SV40 DNA
T2 - effect of intrinsic and drug-induced DNA bending between GC boxes
AU - Sun, Daekyu
AU - Hurley, Laurence H.
N1 - Funding Information:
This research was supported by grants from the Public Health Service (CA-49751), The Upjohn Company, the Welch Foundation and the Burroughs Wellcome Scholars Program. We thank Mr. David Bishop for preparing, proofreading and editing the manuscript.
PY - 1994/11/4
Y1 - 1994/11/4
N2 - The effect of the antitumor antibiotic (+)-CC-1065 on the binding of Spl to the 21-bp repeats of SV40 DNA has been investigated. (+)-CC-1065 alkylates N3 of adenine in DNA and resides in the minor groove. As a consequence of alkylation of the two 5prime;-AGTTA* sequences (* indicates covalent modification site), which reside between GC boxes III and IV, and boxes V and VI, protein binding to the 3prime; sites is completely abolished and there is a significant decrease in Sp1 binding to the other regions. The effect of substituting A5 tracts for the (+)-CC-1065-bonding sequence was intermediate between the unmodified 5prime;-AGTTA* and the drug-modified sequences. It is proposed that a structural distortion of DNA associated with stiffening of the helix induced by the drug-adduct formation is primarily responsible for the inhibition of binding of Spl molecules to 21-bp repeats, rather than steric hindrance due to the occupancy by drug molecules of the minor groove within that region.
AB - The effect of the antitumor antibiotic (+)-CC-1065 on the binding of Spl to the 21-bp repeats of SV40 DNA has been investigated. (+)-CC-1065 alkylates N3 of adenine in DNA and resides in the minor groove. As a consequence of alkylation of the two 5prime;-AGTTA* sequences (* indicates covalent modification site), which reside between GC boxes III and IV, and boxes V and VI, protein binding to the 3prime; sites is completely abolished and there is a significant decrease in Sp1 binding to the other regions. The effect of substituting A5 tracts for the (+)-CC-1065-bonding sequence was intermediate between the unmodified 5prime;-AGTTA* and the drug-modified sequences. It is proposed that a structural distortion of DNA associated with stiffening of the helix induced by the drug-adduct formation is primarily responsible for the inhibition of binding of Spl molecules to 21-bp repeats, rather than steric hindrance due to the occupancy by drug molecules of the minor groove within that region.
KW - (+)-CC-1065
KW - Adenine alkylation
KW - antitumor antibiotic
KW - minor DNA groove binding
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U2 - 10.1016/0378-1119(94)90425-1
DO - 10.1016/0378-1119(94)90425-1
M3 - Article
C2 - 7958981
AN - SCOPUS:0027999874
VL - 149
SP - 165
EP - 172
JO - Gene
JF - Gene
SN - 0378-1119
IS - 1
ER -