Plasmacytoid tumours in mice and Burkitt's lymphomas in humans display characteristic chromosomal translocations involving the c-myc proto-oncogene. Models to explain quantitative changes in c-myc expression have been proposed based on the loss of normal promoters as a result of translocation. However, alternative explanations, such as somatic mutation are needed to explain altered c-myc expression in the absence of gene breakage. We present here the nucleotide sequence of the normal murine c-myc gene. Comparison of this sequence with that of a translocated c-myc gene from a murine plasmacytoma reveals complete identity of coding sequence. One nucleotide difference was found in the non-coding first exon. This shows that qualitative changes of the c-myc gene product are not required for oncogenesis in murine plasmacytomas. In contrast, mutations are found in coding and non-coding regions of translocated c-myc genes from Burkitt's lymphomas, suggesting that the mechanisms by which c-myc is activated in plasmacytomas and Burkitt's lymphomas are different.

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An affinity column for isolating Z-DNA binding proteins was made by attaching brominated poly(dG-dC) to Sephadex. Proteins from Drosophila nuclei were prepared and those that could bind to Escherichia coli B-DNA were removed from the solution. The remaining proteins were passed over the Z-DNA affinity column and then eluted with NaCl. Using both direct and competitive filter binding assays, we found that the eluted proteins bind to brominated poly(dG-dC) (Z-DNA) and poly(dG-m5dC) but not to poly(dG-dC) (B-DNA), native or denatured E. coli or calf thymus DNA, or brominated oligonucleotides. The proteins also bind to negatively supercoiled plasmids carrying Z-DNA sequences but not to relaxed or linearized plasmids in which the Z-DNA conformation is no longer present. Gel analysis reveals a mixture of several large proteins up to approximately 150,000 daltons.Z-DNA is a left-handed conformation ofthe double helix which is favored by segments having alternations in purine and pyrimidine base sequences (1). Z-DNA is stabilized in poly(dGdC) by high concentrations of NaCl and somewhat lower concentrations of MgCl2 (2, 3). It is also stabilized by chemical modifications including methylation of cytosine at C5 (4) or bromination of poly(dG-dC) at guanine C8 and cytosine C5 (5). Brominated poly(dG-dC) is found as Z-DNA in a low-salt medium because the bromine atom stabilizes the guanine residues in the syn conformation which is found in alternate residues in Z-DNA, in contrast to the anti conformation which is found throughout in right-handed B-DNA. The brominated polymer has been used to induce the production ofantibodies which are specific for left-handed Z-DNA (5). These antibodies have been used to identify Z-DNA in various organisms, including the polytene chromosome of Drosophila (6), the macronucleus of the ciliated protozoan Stylonichia (7), and certain plant nuclei (unpublished data). The left-handed Z-DNA conformation is also stabilized by negative supercoiling (8-10). The specificity of the antibodies for Z-DNA has also been demonstrated recently by their ability to combine with identified Z-DNA segments of negatively supercoiled plasmids but not with relaxed plasmids (10).If Z-DNA plays a role in biological systems, it is likely to do so through the use of proteins, some ofwhich should bind specifically to Z-DNA and not to B-DNA. Such proteins could have various roles in biological systems, including the stabilization of Z-DNA conformation. Because of our earlier demonstration of Z-DNA in Drosophila polytene chromosomes (6), we chose to undertake the isolation of Z-DNA binding proteins from that organism. We have used this method ofaffinity chromatography (11). Here we report the isolation of a group of proteins from Drosophila which have the property of binding selectively to Z-DNA. The proteins are large-up to 150,000 daltons. They bind to poly(dG-dC) when it is in the Z-DNA form but not when it is in the B-DNA form. Furthermore, they bind to negatively supercoiled plasmids under conditions such th...