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Title: A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
Author: Benabou Zdaou, Sanae
Mazzini, Stefania
Aviñó Andrés, Anna
Eritja i Casadellà, Ramon
Gargallo Gómez, Raimundo
Keywords: Tumors
Àcids nucleics
Nucleic acids
Issue Date: 1-Nov-2019
Publisher: Nature Publishing Group
Abstract: Some lung and ovarian tumors are connected to the loss of expression of SMARCA4 gene. In its promoter region, a 44-nucleotides long guanine sequence prone to form G-quadruplex structures has been studied by means of spectroscopic techniques (circular dichroism, molecular absorption and nuclear magnetic resonance), size exclusion chromatography and multivariate analysis. The results have shown that the central 21-nucleotides long sequence comprising four guanine tracts of disparate length is able to fold into a pH-dependent ensemble of G-quadruplex structures. Based on acid-base titrations and melting experiments of wild and mutated sequences, the formation of a C·C+ base pair between cytosine bases present at the two lateral loops is shown to promote a reduction in conformational heterogeneity, as well as an increase in thermal stability. The formation of this base pair is characterized by a pKa value of 7.1±0.2 at 20 oC and 150 mM KCl. This value, higher than those usually found in i-motif structures, is related to the additional stability provided by guanine tetrads in the G-quadruplex. To our knowledge, this is the first thermodynamic description of this base pair in loops of antiparallel G-quadruplex structures.
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It is part of: Scientific Reports, 2019, vol. 9, p. 15807
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Enginyeria Química i Química Analítica)

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