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dc.contributor.authorColizzi, Francesco
dc.contributor.authorPerez-Gonzalez, Cibran
dc.contributor.authorFritzen, Remi
dc.contributor.authorLevy, Yaakov
dc.contributor.authorWhite, Malcolm F.
dc.contributor.authorPenedo, J. Carlos
dc.contributor.authorBussi, Giovanni
dc.date.accessioned2019-10-21T08:30:28Z
dc.date.available2019-10-21T08:30:28Z
dc.date.issued2019-11-05
dc.identifier.citationColizzi , F , Perez-Gonzalez , C , Fritzen , R , Levy , Y , White , M F , Penedo , J C & Bussi , G 2019 , ' Asymmetric base-pair opening drives helicase unwinding dynamics ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 116 , no. 45 , pp. 22471-22477 . https://doi.org/10.1073/pnas.1901086116en
dc.identifier.issn0027-8424
dc.identifier.otherPURE: 261540565
dc.identifier.otherPURE UUID: d7604670-ce7a-4053-9b6c-fcfee7c369cc
dc.identifier.otherORCID: /0000-0003-1543-9342/work/63716502
dc.identifier.otherORCID: /0000-0003-3457-8364/work/63716900
dc.identifier.otherScopus: 85074462526
dc.identifier.otherPubMed: 31628254
dc.identifier.otherORCID: /0000-0002-5807-5385/work/74872769
dc.identifier.otherWOS: 000494457400017
dc.identifier.urihttps://hdl.handle.net/10023/18714
dc.descriptionF.C. thanks Laurène Bastet, Gaston Giroux, and the Bibliothèque Roger-Maltais at UdeS for providing infrastructures and support. F.C. acknowledges sabbatical funding (2013 to 2015) from Romano Colizzi and Maria Gaudio in Taranto, Italy, and has received support by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant 752415. C.P.-G. thanks the Engineering and Physical Sciences Research Council (EPSRC) and the University of St. Andrews for financial support. Work in M.F.W. and J.C.P.’s laboratories was supported by Grant 091825/Z/10/Z from the Wellcome Trust. G.B.’s laboratory has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant 306662, S-RNA-S.en
dc.description.abstractThe opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.
dc.format.extent7
dc.language.isoeng
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen
dc.rightsCopyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).en
dc.subjectDouble helixen
dc.subjectNucleic acidsen
dc.subjectSimulationsen
dc.subjectExperimentsen
dc.subjectUnwindabilityen
dc.subjectQH301 Biologyen
dc.subjectQH426 Geneticsen
dc.subjectDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccQH301en
dc.subject.lccQH426en
dc.titleAsymmetric base-pair opening drives helicase unwinding dynamicsen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.sponsorThe Wellcome Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Physics and Astronomyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.identifier.doihttps://doi.org/10.1073/pnas.1901086116
dc.description.statusPeer revieweden
dc.identifier.urlhttps://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1901086116/-/DCSupplementalen
dc.identifier.grantnumber091825/Z/10/Zen
dc.identifier.grantnumber091825/Z/10/Zen


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