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 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Genetics

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