Binding of Sp1 to the 21-bp repeat region of SV40 DNA

effect of intrinsic and drug-induced DNA bending between GC boxes

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalGene
Volume149
Issue number1
DOIs
StatePublished - Nov 4 1994
Externally publishedYes

Fingerprint

CC 1065
DNA
Pharmaceutical Preparations
Alkylation
Adenine
Protein Binding
Anti-Bacterial Agents

Keywords

  • (+)-CC-1065
  • Adenine alkylation
  • antitumor antibiotic
  • minor DNA groove binding

ASJC Scopus subject areas

  • Genetics

Cite this

@article{85a5cca6f8124d429a76f7b7bec3a7aa,
title = "Binding of Sp1 to the 21-bp repeat region of SV40 DNA: effect of intrinsic and drug-induced DNA bending between GC boxes",
abstract = "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.",
keywords = "(+)-CC-1065, Adenine alkylation, antitumor antibiotic, minor DNA groove binding",
author = "Daekyu Sun and Laurence Hurley",
year = "1994",
month = "11",
day = "4",
doi = "10.1016/0378-1119(94)90425-1",
language = "English (US)",
volume = "149",
pages = "165--172",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0027999874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027999874&partnerID=8YFLogxK

U2 - 10.1016/0378-1119(94)90425-1

DO - 10.1016/0378-1119(94)90425-1

M3 - Article

VL - 149

SP - 165

EP - 172

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1

ER -