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Research Overview

Unusual DNA structures, Including DNA Triplexes

More than two decades ago, we have characterized an unusual three-stranded DNA structure - H-DNA, or triplex - formed by homopurine-homopyrimidine mirror repeats.

Mirkin Fig 3

Figure 3. The structure of the triple stranded H-DNA. The two complementary strands of a homopurinehomopyrimidine repeat are colored in red and gray, while flanking DNA is colored green. The structure is called H-y when the red strand is homopyrimide, and H-r if when it is homopurine. One can see
that the red and green strands in this structure are not linked, i.e. formation of H-DNA is topologically equivalent to an unwinding of the entire homopurine-homopyrimidine repeat.

Little did we know at a time that one of those repeats, (GAA)n/(TTC)n, will be eventually implicated in the development of a hereditary human disorder - Friedreich's ataxia. We have since found that formation of unusual DNA structures by H motifs during the DNA synthesis in vitro could block various DNA polymerases. Remarkably, the polymerase itself triggered the formation of an unusual DNA structure that subsequently inhibited it. Simple DNA repeats including, but not limited to H motifs were thus called "suicidal sequences" for the DNA polymerization. It has now become apparent that various DNA repeats could serve as suicidal motifs for the RNA polymerase, as well. Considerable efforts are currently being devoted to the detection of DNA triplexes and other unusual DNA structures inside living cells and elucidating their biological roles in norm and disease.