While no definitive biological significance of Z-DNA has been found, it 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.[1]
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.[2]
Z-DNA sequences downstream 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, Z-DNA is unlikely to form nucleosomes, which are often located after a Z-DNA forming sequence. Because of this property, Z-DNA is hypothesized to code for nucleosome positioning. Since the placement of nucleosomes influences the binding of transcription factors, Z-DNA is thought to regulate the rate of transcription.[3]
Z-DNA formation via active transcription has been shown to increase genetic instability, creating a propensity towards mutagenesis. A study on Escherichia coli found that gene deletions spontaneously occur in plasmids containing Z-DNA-forming sequences.[4] 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.[5]
The toxic effect of ethidium bromide 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.
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Edits by Eunice: However, while supercoiling is associated with both transcription and DNA replication (I suggest changing wording to "DNA replication and transcription"), Z-DNA formation is primarily linked to the rate of transcription (change to "transcription rate")
Nucleosomes (regions of DNA tightly wrapped around histone proteins) are unlikely to form on Z-DNA but often occur after a Z-DNA forming sequence. (instead of defining nucleosomes, add the link for the wikipedia page).
This regulates the rate of transcription in certain regions of DNA. (Vague what you are referring to as "this")
Nathan's Edits:
A comparison of regions with a high sequence-dependent, predicted propensity to form Z-DNA in human chromosome 22 with a selected set of known gene transcription sites supports this correlation.
For this sentence, adding "supports this correlation" is sort a sloppy way to connect it to the previous sentence, maybe find a better way to link these two sentences together.
Z-DNA sequences downstream of promoter regions stimulate transcription, with the greatest increase in activity observed for Z-DNA placed three helical turns after the promoter sequence
The "with the greatest increase in activity observed for Z-DNA placed three helical turns" sounds a little clunky.
Because of this property, Z-DNA can be thought of as a code for nucleosome positioning, thus controlling which regions of DNA can be more easily opened for transcription. This regulates the rate of transcription in certain regions of DNA.
These two sentences can be combined, also the "can be thought of as a code for" can be replaced with a more succinct "can act as a code", and the "can be more easily opened" sounds a little too wordy.
- ^ Wittig; et al. (1991). "Transcription is associated with Z-DNA formation in metabolically active permeabilized mammalian cell nuclei". Proceedings of the National Academy of Sciences. 88 (6): 2259–2263. doi:10.1073/pnas.88.6.2259. PMID 2006166.
- ^ Champ; et al. (2004). "Distributions of Z-DNA and nuclear factor I in human chromosome 22: a model for coupled transcriptional regulation". Nucleic Acids Res. 32 (22): 6501–6510. doi:10.1093/nar/gkh988. PMID 15598822.
- ^ Wong; et al. (2007). "Characterization of Z-DNA as a nucleosome-boundary element in yeast Saccharomyces cerevisiae". Proceedings of the National Academy of Sciences. 104 (7): 2229–2234. doi:10.1073/pnas.0611447104. PMID 17284586.
- ^ 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.
- ^ 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.