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Inferring the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii.

Author(s): Böndel KB, Kraemer SA, Samuels T, McClean D, Lachapelle J, Ness RW, Colegrave N, Keightley PD

PLoS Biol. 2019 Jun 26;17(6):e3000192 Authors: Böndel KB, Kraemer SA, Samuels T, McClean D, Lachapelle J, Ness RW, Colegrave N, Keightley PD

Article GUID: 31242179
Stabilization of i-motif structures by 2'-β-fluorination of DNA.

Author(s): Assi HA, Harkness RW, Martin-Pintado N, Wilds CJ, Campos-Olivas R, Mittermaier AK, González C, Damha MJ

Nucleic Acids Res. 2016 06 20;44(11):4998-5009 Authors: Assi HA, Harkness RW, Martin-Pintado N, Wilds CJ, Campos-Olivas R, Mittermaier AK, González C, Damha MJ

Article GUID: 27166371
Title:Stabilization of i-motif structures by 2'-β-fluorination of DNA.
Authors:Assi HA,  Harkness RW,  Martin-Pintado N,  Wilds CJ,  Campos-Olivas R,  Mittermaier AK,  González C,  Damha MJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/27166371?dopt=Abstract
DOI:10.1093/nar/gkw402
Category:Nucleic Acids Res
PMID:27166371
Dept Affiliation: CHEMBIOCHEM
1 Department of Chemistry, McGill University, Montreal, QC H3A 0B8, Canada.
2 Instituto de Química Física 'Rocasolano', CSIC, 28006 Madrid, Spain.
3 Department of Chemistry, McGill University, Montreal, QC H3A 0B8, Canada Department of Chemistry and Biochemistry, Concordia University, Montreal, QC H4B 1R6, Canada.
4 Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
5 Instituto de Química Física 'Rocasolano', CSIC, 28006 Madrid, Spain cgonzalez@iqfr.csic.es.
6 Department of Chemistry, McGill University, Montreal, QC H3A 0B8, Canada masad.damha@mcgill.ca.

Description:

Stabilization of i-motif structures by 2'-ß-fluorination of DNA.

Nucleic Acids Res. 2016 06 20;44(11):4998-5009

Authors: Assi HA, Harkness RW, Martin-Pintado N, Wilds CJ, Campos-Olivas R, Mittermaier AK, González C, Damha MJ

Abstract

i-Motifs are four-stranded DNA structures consisting of two parallel DNA duplexes held together by hemi-protonated and intercalated cytosine base pairs (C:CH(+)). They have attracted considerable research interest for their potential role in gene regulation and their use as pH responsive switches and building blocks in macromolecular assemblies. At neutral and basic pH values, the cytosine bases deprotonate and the structure unfolds into single strands. To avoid this limitation and expand the range of environmental conditions supporting i-motif folding, we replaced the sugar in DNA by 2-deoxy-2-fluoroarabinose. We demonstrate that such a modification significantly stabilizes i-motif formation over a wide pH range, including pH 7. Nuclear magnetic resonance experiments reveal that 2-deoxy-2-fluoroarabinose adopts a C2'-endo conformation, instead of the C3'-endo conformation usually found in unmodified i-motifs. Nevertheless, this substitution does not alter the overall i-motif structure. This conformational change, together with the changes in charge distribution in the sugar caused by the electronegative fluorine atoms, leads to a number of favorable sequential and inter-strand electrostatic interactions. The availability of folded i-motifs at neutral pH will aid investigations into the biological function of i-motifs in vitro, and will expand i-motif applications in nanotechnology.

PMID: 27166371 [PubMed - indexed for MEDLINE]