Thermal and pH Stabilities of i-DNA: Confronting in vitro Experiments with Models and In-Cell NMR Data

Mingpan Cheng; Dehui Qiu; Liezel Tamon; Eva Ištvánková; Pavlína Víšková; Samir Amrane; Aurore Guédin; Jielin Chen; Laurent Lacroix; Huangxian Ju; Lukáš Trantírek; Aleksandr B Sahakyan; Jun Zhou; Jean-Louis Mergny

doi:10.1002/anie.202016801

Thermal and pH Stabilities of i-DNA: Confronting in vitro Experiments with Models and In-Cell NMR Data

Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10286-10294. doi: 10.1002/anie.202016801. Epub 2021 Mar 24.

Authors

Mingpan Cheng^{1

2}, Dehui Qiu¹, Liezel Tamon³, Eva Ištvánková⁴, Pavlína Víšková⁴, Samir Amrane², Aurore Guédin², Jielin Chen¹, Laurent Lacroix⁵, Huangxian Ju¹, Lukáš Trantírek⁴, Aleksandr B Sahakyan³, Jun Zhou¹, Jean-Louis Mergny^{1

2

6}

Affiliations

¹ State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, China.
² ARNA Laboratory, Université de Bordeaux, INSERM U 1212, CNRS UMR5320, IECB, 33607, Pessac, France.
³ MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
⁴ Central European Institute of Technology, Masaryk University, 62500, Brno, Czech Republic.
⁵ IBENS, Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005, Paris, France.
⁶ Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, 91128, Palaiseau, France.

PMID: 33605024
DOI: 10.1002/anie.202016801

Abstract

Recent studies indicate that i-DNA, a four-stranded cytosine-rich DNA also known as the i-motif, is actually formed in vivo; however, a systematic study on sequence effects on stability has been missing. Herein, an unprecedented number of different sequences (271) bearing four runs of 3-6 cytosines with different spacer lengths has been tested. While i-DNA stability is nearly independent on total spacer length, the central spacer plays a special role on stability. Stability also depends on the length of the C-tracts at both acidic and neutral pHs. This study provides a global picture on i-DNA stability thanks to the large size of the introduced data set; it reveals unexpected features and allows to conclude that determinants of i-DNA stability do not mirror those of G-quadruplexes. Our results illustrate the structural roles of loops and C-tracts on i-DNA stability, confirm its formation in cells, and allow establishing rules to predict its stability.

Keywords: DNA; i-motif; intracellular stability; pH transition; thermal stability.

Publication types

Research Support, Non-U.S. Gov't