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Review
. 2022 Sep 5:13:959258.
doi: 10.3389/fgene.2022.959258. eCollection 2022.

Non-canonical DNA structures: Diversity and disease association

Aparna Bansal  1   2 , Shikha Kaushik  1   3 , Shrikant Kukreti  1
Affiliations
Review

Non-canonical DNA structures: Diversity and disease association

Aparna Bansal et al. Front Genet. .

Abstract

A complete understanding of DNA double-helical structure discovered by James Watson and Francis Crick in 1953, unveil the importance and significance of DNA. For the last seven decades, this has been a leading light in the course of the development of modern biology and biomedical science. Apart from the predominant B-form, experimental shreds of evidence have revealed the existence of a sequence-dependent structural diversity, unusual non-canonical structures like hairpin, cruciform, Z-DNA, multistranded structures such as DNA triplex, G-quadruplex, i-motif forms, etc. The diversity in the DNA structure depends on various factors such as base sequence, ions, superhelical stress, and ligands. In response to these various factors, the polymorphism of DNA regulates various genes via different processes like replication, transcription, translation, and recombination. However, altered levels of gene expression are associated with many human genetic diseases including neurological disorders and cancer. These non-B-DNA structures are expected to play a key role in determining genetic stability, DNA damage and repair etc. The present review is a modest attempt to summarize the available literature, illustrating the occurrence of non-canonical structures at the molecular level in response to the environment and interaction with ligands and proteins. This would provide an insight to understand the biological functions of these unusual DNA structures and their recognition as potential therapeutic targets for diverse genetic diseases.

Keywords: G-quadruplex; Z-DNA; cruciform; non-canonical DNA; triplex.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of DNA non-canonical structures and the diseases associated.
FIGURE 2
FIGURE 2
(A) Sugar pucker in DNA (i) C2′-endo and (ii) C3′-endo. (B) N-glycosidic bond conformations in DNA (i) syn and (ii) anti.
FIGURE 3
FIGURE 3
Schematic representation of (A) Watson–Crick, (B) Hoogsteen, (C) reverse Watson–Crick, and (D) reverse Hoogsteen hydrogen bonding patterns.
FIGURE 4
FIGURE 4
Structure of B-DNA and non-B-DNA.
FIGURE 5
FIGURE 5
Helical representation of (A) intramolecular and (B) intermolecular DNA triplex.
FIGURE 6
FIGURE 6
Possibilities of intramolecular triplex formation (H/*H-DNA).
FIGURE 7
FIGURE 7
Hydrogen bonding pattern involved in DNA triplexes (A) pyrimidine motif and (B) purine motif.
FIGURE 8
FIGURE 8
Possibilities of intermolecular triplex formation.
FIGURE 9
FIGURE 9
Schematic represent of (A) central dogma of molecular biology, (B) antigene, and (C) antisense strategy.
FIGURE 10
FIGURE 10
Schematic representation of role of different non-B-DNA structures in inducing genomic instability.
FIGURE 11
FIGURE 11
Triplex formation inhibits the gene expression by (i) promoter occlusion, (ii) inhibiting transcription initiation, and (iii) blocking RNA polymerase.
FIGURE 12
FIGURE 12
Different topologies adopted by a G-quadruplex structure.
FIGURE 13
FIGURE 13
Different topologies of i-motif DNA structures.
See this image and copyright information in PMC

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