The Structural and Functional Properties of Z-DNA

Заварыкина, Т. М.; Atkarskaya, M V; Zhizhina, G. P.

doi:10.1134/s0006350919050270

Cited by 5 publications

(4 citation statements)

References 103 publications

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“…Whether the host immune system directly reconciles an abundance of Z-DNA in the EPS of bacterial biofilms has yet to be shown, although there is ample evidence for the involvement of Z-DNA-binding proteins in the innate immune response and host-pathogen interactions (Feng et al, 2011;Kim et al, 2003;Kwon and Rich, 2005;Oh et al, 2002;Ray et al, 2013;Shin et al, 2016;Szczesny et al, 2018;van der Vorst et al, 2018;Wang et al, 2006;Zavarykina et al, 2019). We propose that bacterial-derived Z-DNA within biofilms is a major contributor to the reservoir of Z-DNA within the host.…”

Section: Discussionmentioning

confidence: 87%

“…Conversely, Z-DNA has a left-handed configuration with distinct nucleotide geometry but preserves Watson-Crick base-pairing, is resistant to nuclease degradation (Ramesh and Brahmachari, 1989), and is not abundant intracellularly due to its high intrinsic energy state (Dumat et al, 2016;Ho et al, 1991;Kim et al, 2018). However, Z-DNA-forming sequences are involved in multiple intracellular transactions (Zavarykina et al, 2019;Shin et al, 2016;Zhou et al, 2009;Ray et al, 2013;Wang et al, 2006;van der Vorst et al, 2018). Additionally, Z-DNA binding proteins, although rare, are involved in gene regulation (Oh et al, 2002), viral pathogenesis (e.g., E3L) (Kim et al, 2003;Kwon and Rich, 2005), innate immune sensing (e.g., ZBP1) (Kuriakose and Kanneganti, 2018;Newton et al, 2016), DNA recognition (e.g., ADAR-1) (Kim et al, 2000), and inflammation (Szczesny et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

Buzzo

Devaraj

Gloag

et al. 2021

Cell

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

Buzzo

Devaraj

Gloag

et al. 2021

Cell

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“…As it was shown by us and others based on sequence analysis alone ( 18,19,24,27,35,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54) ), Zflipons are enriched in promoters. Here we find Z-flipon enrichment in conserved humanmouse sequences is even higher and we found common pattern of omics features colocalized with conserved Z-flipons at bidirectional promoters.…”

Section: Z-flipons Enrichment At Alternative and Bidirectional Promotersmentioning

confidence: 67%

Z-DNA formation in promoters conserved between human and mouse are associated with increased transcription initiation rates

Popstova,

Herbert,

Beknazarov

et al. 2024

Preprint

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A long-standing question concerns the role of Z-DNA in transcription. Here we use a deep learning approach DeepZ that predicts Z-flipons based on DNA sequence, structural properties of nucleotides and omics data. We examined Z-flipons that are conserved between human and mouse genomes after generating whole-genome Z-flipon map and then validated them by orthogonal approaches based on high resolution chemical mapping of Z-DNA and the transformer algorithm Z-DNABERT. For human and mouse, we revealed similar pattern of transcription factors, chromatin remodelers, and histone marks associated with conserved Z-flipons. We found significant enrichment of Z-flipons in alternative and bidirectional promoters associated with neurogenesis genes. We show that conserved Z-flipons are associated with increased experimentally determined transcription initiation rates compared to promoters without Z-flipons, but without affecting elongation or pausing. Our findings support a model where Z-flipons impact phenotype by regulating the reset of preinitiation complexes.

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“…30 Z-DNA (linked to cancer, autoimmune and neurological diseases) is produced in vivo during the transcription process as a result of torsional strains generated by RNA polymerase moving along the sequence of the DNA double helix. 31 32 This provides a range of possible intermolecular interactions, including irreversible covalent binding, reversible groove interactions, or intercalation between metal complexes and DNA, due to the structural complexity and polymorphism of DNA. Studies on the effect of DNA metal complexes have shown that metal coordination geometry and the ligand configuration can influence binding behavior: square planar metal complexes were observed to have a greater capacity for deeper insertion as an intercalator than complexes with octahedral or tetrahedral geometry.…”

Section: Introductionmentioning

confidence: 99%

Metal Complexes as DNA Synthesis and/or Repair Inhibitors: Anticancer and Antimicrobial Agents

Ngoepe

Clayton

2021

Pharmaceutical Fronts

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Medicinal inorganic chemistry involving the utilization of metal-based compounds as therapeutics has become a field showing distinct promise. DNA and RNA are ideal drug targets for therapeutic intervention in the case of various diseases, such as cancer and microbial infection. Metals play a vital role in medicine, with at least 10 metals known to be essential for human life and a further 46 nonessential metals having been involved in drug therapies and diagnosis. These metal-based complexes interact with DNA in various ways, and are often delivered as prodrugs which undergo activation in vivo. Metal complexes cause DNA crosslinking, leading to the inhibition of DNA synthesis and repair. In this review, the various interactions of metal complexes with DNA nucleic acids, as well as the underlying mechanism of action, were highlighted. Furthermore, we also discussed various tools used to investigate the interaction between metal complexes and the DNA. The tools included in vitro techniques such as spectroscopy and electrophoresis, and in silico studies such as protein docking and density-functional theory that are highlighted for preclinical development.

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The Structural and Functional Properties of Z-DNA

Cited by 5 publications

References 103 publications

Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

Z-DNA formation in promoters conserved between human and mouse are associated with increased transcription initiation rates

Metal Complexes as DNA Synthesis and/or Repair Inhibitors: Anticancer and Antimicrobial Agents

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