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Left-handed Z-DNA: structure and function.

Abstract

Z-DNA is a high energy conformer of B-DNA that forms in vivo during transcription as a result of torsional strain generated by a moving polymerase. An understanding of the biological role of Z-DNA has advanced with the discovery that the RNA editing enzyme double-stranded RNA adenosine deaminase type I (ADAR1) has motifs specific for the Z-DNA conformation. Editing by ADAR1 requires a double-stranded RNA substrate. In the cases known, the substrate is formed by folding an intron back onto the exon that is targeted for modification. The use of introns to direct processing of exons requires that editing occurs before splicing. Recognition of Z-DNA by ADAR1 may allow editing of nascent transcripts to be initiated immediately after transcription, ensuring that editing and splicing are performed in the correct sequence. Structural characterization of the Z-DNA binding domain indicates that it belongs to the winged helix-turn-helix class of proteins and is similar to the globular domain of histone-H5.

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BibTeXRIS

A Herbert, A Rich. 1999. Left-handed Z-DNA: structure and function.. https://doi.org/10.1023/a%3A1003768526018

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5',8-cyclo-dAdo and 8-oxo-dAdo DNA Lesions Are Both Substrates of Adenosine Deaminase: A Preliminary Study.

Genetic information, whether inside or outside the nucleus, is exposed to a variety of harmful physico-chemical factors. Although DNA damage repair systems have been extensively studied, little information about post-repair and non-genomic DNA damage metabolism is available in the literature. Adenosine deaminase (ADA) is an abundant enzyme found on both sides of the cell membrane that regulates the concentration of adenine derivatives. In this article, it has been shown that 7,8-dihydro-8-oxo-2'-deoxyadenosine (OXOdAdo) and (5'R/S) 5',8-cyclo-2'-deoxyadenosine ((5'R/S)cdAdo) are suitable substrates for ADA. For this purpose, theoretical Density Functional Tight Binding and RP-HPLC analyses were applied. The products of ADA activity, i.e., OXOdIno (7,8-dihydro-8-oxo-2'-deoxyinosine) and (5'R/S) cdIno ((5'R/S) 8-cyclo-2'-deoxyinosine), were identified and confirmed by high-resolution mass spectroscopy. Although the (5'R) and (5'S)cdAdo enzymatic deamination processes are much slower (34% and 32% after 168 h, respectively) than the process observed for dAdo, 5',8-cyclo-2'-deoxyinosine should be considered when monitoring cyclopurine levels in physiological fluids. The same should be considered in the case of OXOdAdo, which is completely converted to OXOdIno within one minute and may therefore be less visible than OXOdGuo during mass spectroscopy analysis. Both these observations are important, given the abundance of 2'-deoxyadenosine on both sides of the cell membrane and its potential conversion into OXOdAdo and (5'R/S)cdAdo. They may also explain why the observed level of OXOdAdo is much lower than that of OXOdGuo in cells and physiological fluids, even though their difference in ionisation potential is only 0.25 eV. Future studies are needed to further investigate the metabolism of DNA damage and to identify the enzymes involved in nucleic acid biochemistry.

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