Topology and Formation of Triple-Stranded H-DNA

Abstract

Repeating copolymers of (dT-dC)n.(dA-dG)n sequences (TC.AGn) can assume a hinged DNA structure (H-DNA) which is composed of triple-stranded and single-stranded regions. A model for the formation of H-DNA is proposed, based on two-dimensional gel electrophoretic analysis of DNA's with different lengths of (TC.AG)n copolymers. In this model, H-DNA formation is initiated at a small denaturation bubble in the interior of the copolymer, which allows the duplexes on either side to rotate slightly and to fold back, in order to make the first base triplet. This nucleation establishes which of several nonequivalent H-DNA conformations is to be assumed by any DNA molecule, thereby trapping each molecule in one of several metastable conformers that are not freely interconvertible. Subsequently, the acceptor region spools up single-stranded polypyrimidines as they are released by progressive denaturation of the donor region; both the spooling and the denaturation result in relaxation of negative supercoils in the rest of the DNA molecule. From the model, it can be predicted that the levels of supercoiling of the DNA determine which half of the (dT-dC)n repeat is to become the donated third strand.