(+)‐CC‐1065 as a probe for intrinsic and protein‐induced bending of DNA

Research output: Contribution to journalReview article

7 Scopus citations

Abstract

(+)‐CC ‐1065 is biologically potent DNA‐reactive antitumor antibiotic produced by Streptomyces zelensis. This antibiotic covalently modifies DNA by alkylation of N‐3 of a adenine in the minor groove. As a Structural consequence of covalent modification of DNA, the helix axis id bent into the minor groove. The drug‐induced bending of DNA has similarities to intrinsic. A‐tract bending and the 3′ adenine of A‐tracts shows a unique reactivity to alkylation by (+) ‐CC‐1065. Upon covalent modification of A‐tracts, the magnitude of bending is increased and helix is stiffened. Using high‐field NMR, hydroxyl‐radical footprinting and gel electrophoresis, the molecular basis for the high reactivity of the bonding sequence 5′ ‐ AGTTA* (an asterisk indicates the covalent modification site) to (+)‐CC‐1065 has been shown to involve the inherent conformational flexibility of this sequence. Furthermore, these studies also demonstrate that after alkylation the drug‐induced bending is focused over the TT region. By analogy with the junction bend model for A‐tracts, a ‘truncated junction bend model’ is proposed for this structure. Last, the application of (+)‐CC‐1065 entrapped/induced bending of DNA as a probe for the Sp1‐induced bending of the 21‐base‐pair repeat an Mu transpose bending of the att L3 sequence is described.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalJournal of Molecular Recognition
Volume7
Issue number2
DOIs
StatePublished - Jun 1994
Externally publishedYes

Keywords

  • (+)‐CC‐1065
  • DNA bending
  • Mu transpose
  • Sp1

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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