Evidence map›Paper›PMID 38281263›Full record

ArticleNucleic acids research2024

NMR measurements of transient low-populated tautomeric and anionic Watson-Crick-like G·T/U in RNA:DNA hybrids: implications for the fidelity of transcription and CRISPR/Cas9 gene editing.

Or Szekely, Atul Kaushik Rangadurai, Stephanie Gu, Akanksha Manghrani, Serafima Guseva, Hashim M Al-Hashimi

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Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

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0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Or SzekelyDepartment of Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-9502-9337
Atul Kaushik RangaduraiDepartment of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Stephanie GuDepartment of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Akanksha ManghraniDepartment of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Serafima GusevaDepartment of Biochemistry and Molecular Biophysics, Columbia University, NY, NY 10032, USA.
Hashim M Al-HashimiDepartment of Biochemistry and Molecular Biophysics, Columbia University, NY, NY 10032, USA.

Funding

Role of DNA structural dynamics in mutagenesis and oncogenesisR01GM089846 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Hashim M Al-Hashimi · 2010 to 2026
$5.2M
Acquisition of 700 MHz NMR SpectrometerS10OD018509 · OD · NEW YORK STRUCTURAL BIOLOGY CENTER · PI PALMER, ARTHUR G · 2015 to 2015
$1.1M
NIH HHS R01GM089846NIH HHS S10 OD018509
6 · The paper itself

Abstract

Many biochemical processes use the Watson-Crick geometry to distinguish correct from incorrect base pairing. However, on rare occasions, mismatches such as G·T/U can transiently adopt Watson-Crick-like conformations through tautomerization or ionization of the bases, giving rise to replicative and translational errors. The propensities to form Watson-Crick-like mismatches in RNA:DNA hybrids remain unknown, making it unclear whether they can also contribute to errors during processes such as transcription and CRISPR/Cas editing. Here, using NMR R1ρ experiments, we show that dG·rU and dT·rG mismatches in two RNA:DNA hybrids transiently form tautomeric (Genol·T/U $ \mathbin{\lower.3ex\hbox{$\buildrel\textstyle\rightarrow\over {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}}$}}$ G·Tenol/Uenol) and anionic (G·T-/U-) Watson-Crick-like conformations. The tautomerization dynamics were like those measured in A-RNA and B-DNA duplexes. However, anionic dG·rU- formed with a ten-fold higher propensity relative to dT-·rG and dG·dT- and this could be attributed to the lower pKa (ΔpKa ∼0.4-0.9) of U versus T. Our findings suggest plausible roles for Watson-Crick-like G·T/U mismatches in transcriptional errors and CRISPR/Cas9 off-target gene editing, uncover a crucial difference between the chemical dynamics of G·U versus G·T, and indicate that anionic Watson-Crick-like G·U- could play a significant role evading Watson-Crick fidelity checkpoints in RNA:DNA hybrids and RNA duplexes.

Indexed as

CRISPR-Cas SystemsGene EditingNucleic Acid HybridizationBase PairingDNANucleic Acid ConformationRNADNARNA

Identifiers

PMID38281263
PMCPMC10954477

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.