A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor

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 magne...

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Autores: Benabou Zdaou, Sanae, Mazzini, Stefania, Aviñó Andrés, Anna, Eritja i Casadellà, Ramon, Gargallo Gómez, Raimundo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/144207
Acceso en línea:https://hdl.handle.net/2445/144207
Access Level:acceso abierto
Palabra clave:Tumors
Àcids nucleics
Nucleòtids
Nucleic acids
Nucleotides
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spelling A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotorBenabou Zdaou, SanaeMazzini, StefaniaAviñó Andrés, AnnaEritja i Casadellà, RamonGargallo Gómez, RaimundoTumorsÀcids nucleicsNucleòtidsTumorsNucleic acidsNucleotidesSome 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.Nature Publishing Group2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/144207Articles publicats en revistes (Enginyeria Química i Química Analítica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-019-52311-5Scientific Reports, 2019, vol. 9, p. 15807https://doi.org/10.1038/s41598-019-52311-5cc-by (c) Benabou, Sanae et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1442072026-05-27T06:46:51Z
dc.title.none.fl_str_mv A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
title A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
spellingShingle A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
Benabou Zdaou, Sanae
Tumors
Àcids nucleics
Nucleòtids
Tumors
Nucleic acids
Nucleotides
title_short A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
title_full A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
title_fullStr A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
title_full_unstemmed A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
title_sort A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor
dc.creator.none.fl_str_mv Benabou Zdaou, Sanae
Mazzini, Stefania
Aviñó Andrés, Anna
Eritja i Casadellà, Ramon
Gargallo Gómez, Raimundo
author Benabou Zdaou, Sanae
author_facet Benabou Zdaou, Sanae
Mazzini, Stefania
Aviñó Andrés, Anna
Eritja i Casadellà, Ramon
Gargallo Gómez, Raimundo
author_role author
author2 Mazzini, Stefania
Aviñó Andrés, Anna
Eritja i Casadellà, Ramon
Gargallo Gómez, Raimundo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Tumors
Àcids nucleics
Nucleòtids
Tumors
Nucleic acids
Nucleotides
topic Tumors
Àcids nucleics
Nucleòtids
Tumors
Nucleic acids
Nucleotides
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/144207
url https://hdl.handle.net/2445/144207
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-019-52311-5
Scientific Reports, 2019, vol. 9, p. 15807
https://doi.org/10.1038/s41598-019-52311-5
dc.rights.none.fl_str_mv cc-by (c) Benabou, Sanae et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Benabou, Sanae et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Enginyeria Química i Química Analítica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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