A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

Satange, Roshan; Chang, Chung-ke; Hou, Ming-Hon

doi:10.1093/nar/gky561

Cited by 27 publications

(28 citation statements)

References 121 publications

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“…Although these defects are generally associated with increased DNA bendability (see e.g. Vafabakhsh and Ha, 2012; Satange et al , 2018), this might not always be the case, as suggested by recent studies (Rossetti et al ., 2015; Jeong and Kim, 2019). Using MD simulations and nuclear magnetic resonance experiments, Orozco, Gonzalez, and coworkers performed a systematic study of the effect of mismatches on DNA flexibility (Rossetti et al ., 2015).…”

Section: Chemical Modifications and Dna Mechanicsmentioning

confidence: 95%

A molecular view of DNA flexibility

Marín-González

Vilhena

Pérez

et al. 2021

Quart. Rev. Biophys.

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DNA dynamics can only be understood by taking into account its complex mechanical behavior at different length scales. At the micrometer level, the mechanical properties of single DNA molecules have been well-characterized by polymer models and are commonly quantified by a persistence length of 50 nm (~150 bp). However, at the base pair level (~3.4 Å), the dynamics of DNA involves complex molecular mechanisms that are still being deciphered. Here, we review recent single-molecule experiments and molecular dynamics simulations that are providing novel insights into DNA mechanics from such a molecular perspective. We first discuss recent findings on sequence-dependent DNA mechanical properties, including sequences that resist mechanical stress and sequences that can accommodate strong deformations. We then comment on the intricate effects of cytosine methylation and DNA mismatches on DNA mechanics. Finally, we review recently reported differences in the mechanical properties of DNA and double-stranded RNA, the other double-helical carrier of genetic information. A thorough examination of the recent single-molecule literature permits establishing a set of general ‘rules’ that reasonably explain the mechanics of nucleic acids at the base pair level. These simple rules offer an improved description of certain biological systems and might serve as valuable guidelines for future design of DNA and RNA nanostructures.

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Section: Chemical Modifications and Dna Mechanicsmentioning

confidence: 95%

A molecular view of DNA flexibility

Marín-González

Vilhena

Pérez

et al. 2021

Quart. Rev. Biophys.

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“…The small molecules that recognize these mismatched DNA duplexes can induce various degrees of structural deformations, with many having pharmaceutical and/or diagnostic potential (10,11). The presence of unstable mismatches in DNA structures may cause base flipping into extrahelical positions, which itself is an important phenomenon observed upon small molecule ligand binding to DNA duplexes (12–14).…”

Section: Introductionmentioning

confidence: 99%

Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation

Satange

Chuang

Neidle

et al. 2019

Nucleic Acids Research

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DNA mismatches are highly polymorphic and dynamic in nature, albeit poorly characterized structurally. We utilized the antitumour antibiotic CoII(Chro)2 (Chro = chromomycin A3) to stabilize the palindromic duplex d(TTGGCGAA) DNA with two G:G mismatches, allowing X-ray crystallography-based monitoring of mismatch polymorphism. For the first time, the unusual geometry of several G:G mismatches including syn–syn, water mediated anti–syn and syn–syn-like conformations can be simultaneously observed in the crystal structure. The G:G mismatch sites of the d(TTGGCGAA) duplex can also act as a hotspot for the formation of alternative DNA structures with a GC/GA-5′ intercalation site for binding by the GC-selective intercalator actinomycin D (ActiD). Direct intercalation of two ActiD molecules to G:G mismatch sites causes DNA rearrangements, resulting in backbone distortion to form right-handed Z-DNA structures with a single-step sharp kink. Our study provides insights on intercalators-mismatch DNA interactions and a rationale for mismatch interrogation and detection via DNA intercalation.

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“…How to construct and describe mismatched base-pairing interactions in structural details is a key issue for understanding the mechanism of the formation of non–B-DNA and finding effective ways to treat some genetic diseases. Numerous studies have shown that many small-molecule intercalators with pharmaceutical and/or diagnostic potential ( Satange et al, 2018 ; Pages et al, 2019 ) can recognize mismatched DNA or RNA duplexes and induce various degrees of structural deformations. The existence of unstable mismatches in nucleic acid sequences may cause nucleobases flipping into additional helical positions, which itself is a significant phenomenon observed during the binding of small-molecule ligands to DNA or RNA duplexes ( Jourdan et al, 2012 ; Tseng et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

The Research of G–Motif Construction and Chirality in Deoxyguanosine Monophosphate Nucleotide Complexes

Zhu

Wang

et al. 2021

Front. Chem.

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A detailed understanding of the mismatched base-pairing interactions in DNA will help reveal genetic diseases and provide a theoretical basis for the development of targeted drugs. Here, we utilized mononucleotide fragment to simulate mismatch DNA interactions in a local hydrophobic microenvironment. The bipyridyl-type bridging ligands were employed as a mild stabilizer to stabilize the GG mismatch containing complexes, allowing mismatch to be visualized based on X-ray crystallography. Five single crystals of 2′-deoxyguanosine–5′–monophosphate (dGMP) metal complexes were designed and obtained via the process of self-assembly. Crystallographic studies clearly reveal the details of the supramolecular interaction between mononucleotides and guest intercalators. A novel guanine–guanine base mismatch pattern with unusual (high anti)–(high anti) type of arrangement around the glycosidic angle conformations was successfully constructed. The solution state 1H–NMR, ESI–MS spectrum studies, and UV titration experiments emphasize the robustness of this g–motif in solution. Additionally, we combined the methods of single-crystal and solution-, solid-state CD spectrum together to discuss the chirality of the complexes. The complexes containing the g–motif structure, which reduces the energy of the system, following the solid-state CD signals, generally move in the long-wave direction. These results provided a new mismatched base pairing, that is g–motif. The interaction mode and full characterizations of g–motif will contribute to the study of the mismatched DNA interaction.

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A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

Cited by 27 publications

References 121 publications

A molecular view of DNA flexibility

A molecular view of DNA flexibility

Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation

The Research of G–Motif Construction and Chirality in Deoxyguanosine Monophosphate Nucleotide Complexes

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