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Developed by negative supercoiling behind RNA polymerase, Z-DNA formed via active transcription has been shown to increase genetic instability, creating a propensity towards mutagenesis near promoter regions.[1] A study on Escherichia coli found that gene deletions spontaneously occur in plasmid regions containing Z-DNA-forming sequences.[2] 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 breakpoint regions in tumor cells have been plotted around Z-DNA-forming sequences.[1] 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.[1][2]
Escherichia coli
- ^ a b c Wang; et al. (2006). "Z-DNA-forming sequences generate large-scale deletions in mammalian cells". The National Academy of Sciences. 108 (8): 2677–2682. doi:10.1073/pnas.0511084103. PMID 16473937.
- ^ a b Freund, A.M.; et al. (1989). "Z-DNA-forming sequences are spontaneous deletion hot spots". Proceedings of the National Academy of Sciences of the United States of America. 86 (19): 7465–7469. PMID 2552445.