AA mismatched DNAs with a single base difference exhibit a large structural change and a propensity for the parallel-stranded conformation

Lee, Chul-Hyun; Cheong, Hae‐Kap; Cho, Jee-Hyun; Cheong, Chaejoon

doi:10.5355/jast.2010.37

Cited by 4 publications

(5 citation statements)

References 20 publications

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“…TT flanked by CG base pairs, {CtC/GtG}, are known, from NMR measurements, not to be hydrogen bonded, 23 or to contain only a single hydrogen bond. 53 This is consistent with the low Morse potentials 6.80 meV. In {AtC/TtG} a stacked mismatch with weaker bonding was measured, 52,55 for which we obtained 6.47 meV.…”

Section: Discussionsupporting

confidence: 88%

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Melting Temperature Measurement and Mesoscopic Evaluation of Single, Double and Triple DNA Mismatches

Oliveira¹,

Long²,

Brown³

et al. 2020

Preprint

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Unlike the canonical base pairs AT and GC, the molecular properties of mismatches such as hydrogen bondings and stacking interactions are strongly dependent on the identity of the neighbouring base pairs. As a result, due to the sheer number of possible combinations of mismatches and flanking base pairs, only a fraction of these have been studied in varying experiments or theoretical models. Here, we report on the melting temperature measurement and mesoscopic analysis of contiguous DNA mismatches in nearest-neighbours and next-nearest neighbour contexts. A total of 4032 different mismatch combinations, including single, double and triple mismatches were covered. These were compared with 64 sequences containing all combination of canonical base pairs in the same location under the same conditions. The mesoscopic calculation, using the Peyrard-Bishop model, was performed on the set of 4096 sequences, and resulted in estimates of on-site and nearest-neighbour interactions that can be correlated to hydrogen bonding and base stacking. Our results confirm many of the known properties of mismatches, including the peculiar sheared stacking of tandem GA mismatches. More intriguingly, it also reveals that a number of mismatches present strong hydrogen bonding when flanked on both sites by other mismatches.

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Section: Discussionsupporting

confidence: 88%

“…AA mismatches in the contexts {CaC/GaG} and {AaC/TaG} context were found to have a single hydrogen bond 52,53 which compares to Morse potentials of 4.66 meV and 7.73 meV, respectively. Other contexts do not indicate substantial hydrogen bonding, for instance the context {Aaa/Tag} with 4.70 meV, was found not to form hydrogen bonds.…”

Section: Discussionmentioning

confidence: 89%

Melting Temperature Measurement and Mesoscopic Evaluation of Single, Double and Triple DNA Mismatches

Oliveira¹,

Long²,

Brown³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…NMR and thermodynamic studies of A…A mismatch containing DNA duplex offer controversial results. While some of them suggest that A…A mismatch destabilizes[ 18 , 19 , 20 , 21 ] the DNA duplex significantly, the others do not[ 22 ]. Physicochemical studies indicate that A…A mismatch in a GAC repeat adopt several distinct conformations in solution including Z-DNA[ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hitherto , this aspect is not realized as there is no DNA duplex structure with A…A mismatch available with any sequence context. Earlier low-resolution 1D NMR studies on DNA duplexes comprising of A…A mismatch[ 18 , 19 , 20 , 21 , 22 ] offer only minimal information with some of them indicating notable destabilization induced at A…A mismatch site[ 18 , 19 , 20 , 21 ]. Strikingly, it has been shown by circular dichroism study that CAG repeat spectra resembles GA homoduplex but not CCG and CTG[ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Strikingly, it has been shown by circular dichroism study that CAG repeat spectra resembles GA homoduplex but not CCG and CTG[ 32 ]. Propensity of A…A mismatch containing DNA to adopt a parallel DNA duplex is also reported[ 21 ]. However, the possibility of CAG repeat expansion to favor parallel duplex can be ruled out as it forms hairpin structure[ 7 , 8 ], which eventually leads to antiparallel orientation for the two strands of the DNA hairpin stem.…”

Section: Discussionmentioning

confidence: 99%

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Twisting Right to Left: A…A Mismatch in a CAG Trinucleotide Repeat Overexpansion Provokes Left-Handed Z-DNA Conformation

2015

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Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington’s disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canonical DNA duplex. Transition from B-to-Z is due to the mechanistic effect that originates from its pronounced nonisostericity with flanking canonical base pairs facilitated by base extrusion, backbone and/or base flipping. Based on these structural insights we envisage that such an unusual DNA structure of the CAG hairpin stem may have a role in disease pathogenesis. As this is the first study that delineates the influence of a single A…A mismatch in reversing DNA helicity, it would further have an impact on understanding DNA mismatch repair.

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Site-Directed Spin Labeling of DNA Reveals Mismatch-Induced Nanometer Distance Changes between Flanking Nucleotides

et al. 2012

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Multiple forms of DNA damages such as base modifications, double-strand breaks, and mispairings are related to inheritable diseases, cancer, and aging. Here, the structural changes of duplex DNA upon incorporation of mismatched base pairs are examined by EPR spectroscopy. Two ethynyl-7-deaza-2'-deoxyadenosine residues separated by two nucleotides were incorporated in DNA and functionalized with 4-azido-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-azido TEMPO) by the click reaction. Mismatches such as dT·dT or dA·dA mispairs were positioned between these two spin labels in DNA duplexes. Pulse EPR experiments reveal that the mismatch-induced local conformational changes are transmitted to the flanking nucleotides and that the impact of this mismatch depends on the nearest neighbor environment.

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AA mismatched DNAs with a single base difference exhibit a large structural change and a propensity for the parallel-stranded conformation

Cited by 4 publications

References 20 publications

Melting Temperature Measurement and Mesoscopic Evaluation of Single, Double and Triple DNA Mismatches

Melting Temperature Measurement and Mesoscopic Evaluation of Single, Double and Triple DNA Mismatches

Twisting Right to Left: A…A Mismatch in a CAG Trinucleotide Repeat Overexpansion Provokes Left-Handed Z-DNA Conformation

Site-Directed Spin Labeling of DNA Reveals Mismatch-Induced Nanometer Distance Changes between Flanking Nucleotides

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