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Thermal and pH Stabilities of i‐DNA: Confronting in vitro Experiments with Models and In‐Cell NMR Data
Author(s) -
Cheng Mingpan,
Qiu Dehui,
Tamon Liezel,
Ištvánková Eva,
Víšková Pavlína,
Amrane Samir,
Guédin Aurore,
Chen Jielin,
Lacroix Laurent,
Ju Huangxian,
Trantírek Lukáš,
Sahakyan Aleksandr B.,
Zhou Jun,
Mergny JeanLouis
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202016801
Subject(s) - dna , cytosine , thermal stability , stability (learning theory) , chemistry , crystallography , dna sequencing , sequence (biology) , biophysics , chemical physics , computational biology , biology , biochemistry , organic chemistry , computer science , machine learning
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.