Potential Z-DNA forming sequences are highly dispersed in the human genome

Abstract

Recent analyses of the three-dimensional structure of synthetic DNA molecules has revealed the existence of a left-handed double-helical conformation of DNA, called Z-DNA. The Z-DNA structure was first observed in molecules having alternating guanine and cytosine bases, but has now also been shown for molecules of sequence poly(dT-dG) . poly(dC-dA) (refs 4-7). If Z-DNA occurs naturally then it might have quite different reactivities with molecules such as proteins or carcinogens from right-handed B-DNA. The interconversion of sequences between B and Z forms, under the influence, for example, of DNA binding proteins or chemical modification, may be important in regulating DNA function. So far, little data have been published on the occurrence of potential Z-DNA forming sequences in eukaryotic DNA. Here we report the presence of a sequence of 50 alternating dT and dG residues within one of the introns of a human cardiac muscle actin gene. Also, using a probe specific for poly(dT-dG) sequences, we have also found that potential Z-DNA forming sequences are highly repeated in the human genome.