Single Strands, Triple Strands, and Kinks in H-DNA

Abstract

A naturally occurring (dT-dC)18:(dA-dG)18 repeat in the H conformation of DNA was shown to contain single-stranded nucleotides in the center of the TC18 repeat and on one half of the AG18 repeat. These results support the model that H-DNA is a structure containing both triple-stranded and single-stranded regions. The stability of this structure was affected by both pH and the degree of negative supercoiling: at pH 7.6 to 7.7, a high level of supercoiling was needed to keep about half of the molecules in the H conformation; at pH 6 and pH 5, normal levels of supercoiling supported H-DNA; and at pH 4, no supercoiling was required. At mildly alkaline pH, the TC/AG18 repeat assumed a novel conformation called J-DNA that differed from both the B and H forms. A three-dimensional model for the structure of H-DNA is proposed that accounts both for the single-strandedness of the nucleotides and for the influence of supercoiling on H-DNA formation. This model predicts and evidence is presented that H-DNA introduces a sharp kink in the DNA. Moreover, the angle of this kink appears not to be fixed, so that H-DNA is also a hinged-DNA.

DNA triple helices: Biological consequences and therapeutic potential

“…For example, H-DNA, or intramolecular triplex DNA is a structure in which half of the pyrimidine tract swivels its backbone parallel to the purine strand in the underlying duplex, or the purine strand (in *H-DNA) binds to the purine strand of the underlying duplex in an antiparallel orientation, to form a triple helical DNA structure [95]. The complimentary strand remains single stranded [96], and is therefore sensitive to S1 nuclease activity. In an H-DNA structure, the conformation is maintained by T-A*T or C-G*C + Hoogsteen hydrogen bonding in the major groove of the DNA.…”

Identification of two distinct MYC breakpoint clusters and their association with various IGH breakpoint regions in the t(8;14) translocations in sporadic Burkitt-lymphoma

“…This sequence motif can form slippage structures with extruded single-strand loops, and triple helices (H-DNA). 42,43 Secondary structural features of DNA are known to attract activity of the nuclease activity of RAG and AID and may be involved in other nucleases such as topoisomerase II. 44,45 We did not find any significant matches to the V(D)J RSS motif; however, this does not completely rule out its potential role.…”

Characterization of a polypurine/polypyrimidine sequence upstream of the mouse metallothionein-I gene

“…Chemical probes that react with unpaired or unstacked bases have previously been shown to be of value in detecting and evaluating non-B DNA structures (18)(19)(20)(21)(22)(23). CAA reacts with adenine and cytosine to form their respective etheno derivatives when these bases occur in unpaired or unstacked conformations.…”

“…These regions of base unpairing are sensitive to chemical and enzymatic probes that react differentially with single-stranded DNA. Chemical and enzymatic probing allows structural information to be deduced for such sequence elements (18)(19)(20)(21)(22)(23). Stable H-DNA structures require some degree of mirror symmetry and are typically stabilized by negative supercoiling.…”

“…Certain PMRs have been shown to isomerize to H-DNA in vitro under conditions of negative supercoiling and acidic pH (11,(14)(15)(16)(17). H-DNA refers to a family of DNA structures characterized by an intramolecular DNA triplex and accompanying regions of base unpairing.…”