depending on the stage of the disease, with maximal antibodies in the most active stages of SLE. Z-DNA in transcription Z-DNA is commonly believed to provide torsional strain relief during transcription, and it is associated with negative supercoiling. However, while supercoiling is associated with both DNA transcription and replication, Z-DNA formation is primarily linked to the rate of transcription. A study of human chromosome 22 showed a correlation between Z-DNA forming regions and promoter regions for nuclear factor I. This suggests that transcription in some human genes may be regulated by Z-DNA formation and nuclear factor I activation. Z-DNA sequences upstream of promoter regions have been shown to stimulate transcription. The greatest increase in activity is observed when the Z-DNA sequence is placed three helical turns after the promoter sequence. Furthermore, using micrococcal nuclease-crosslinking technique, Z-DNA is unlikely to form nucleosomes, which are often located before and/or after a Z-DNA forming sequence. Because of this property, Z-DNA is hypothesized to code for the boundary in nucleosome positioning. Since the placement of nucleosomes influences the binding of transcription factors, Z-DNA is thought to regulate the rate of transcription. Developed behind the pathway of RNA polymerase through negative supercoiling, Z-DNA formed via active transcription has been shown to increase genetic instability, creating a propensity towards mutagenesis near promoters. A study on Escherichia coli found that gene deletions spontaneously occur in plasmid regions containing Z-DNA-forming sequences. In mammalian cells, the presence of such sequences was found to produce large genomic fragment deletions due to chromosomal double-strand breaks. Both of these genetic modifications have been linked to the gene translocations found in cancers such as leukemia and lymphoma, since breakage regions in tumor cells have been plotted around Z-DNA-forming sequences. However, the smaller deletions in bacterial plasmids have been associated with replication slippage, while the larger deletions associated with mammalian cells are caused by non-homologous end-joining repair, which is known to be prone to error. The toxic effect of ethidium bromide (EtBr) on trypanosomas is caused by shift of their kinetoplastid DNA to Z-form. The shift is caused by intercalation of EtBr and subsequent loosening of DNA structure that leads to unwinding of DNA, shift to Z-form and inhibition of DNA replication. Discovery of the Zα domain The first domain to bind Z-DNA with high affinity was discovered in ADAR1 using an approach developed by Alan Herbert. Crystallographic and NMR studies confirmed the biochemical