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Asymmetric base-pair opening drives helicase unwinding dynamics

The 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-pai...

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Autores principales: Colizzi, Francesco, Perez-Gonzalez, Cibran, Fritzen, Remi, Levy, Yaakov, White, Malcolm F., Penedo, J. Carlos, Bussi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842596/
https://www.ncbi.nlm.nih.gov/pubmed/31628254
http://dx.doi.org/10.1073/pnas.1901086116
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author Colizzi, Francesco
Perez-Gonzalez, Cibran
Fritzen, Remi
Levy, Yaakov
White, Malcolm F.
Penedo, J. Carlos
Bussi, Giovanni
author_facet Colizzi, Francesco
Perez-Gonzalez, Cibran
Fritzen, Remi
Levy, Yaakov
White, Malcolm F.
Penedo, J. Carlos
Bussi, Giovanni
author_sort Colizzi, Francesco
collection PubMed
description The 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.
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spelling pubmed-68425962019-11-15 Asymmetric base-pair opening drives helicase unwinding dynamics Colizzi, Francesco Perez-Gonzalez, Cibran Fritzen, Remi Levy, Yaakov White, Malcolm F. Penedo, J. Carlos Bussi, Giovanni Proc Natl Acad Sci U S A Physical Sciences The 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. National Academy of Sciences 2019-11-05 2019-10-18 /pmc/articles/PMC6842596/ /pubmed/31628254 http://dx.doi.org/10.1073/pnas.1901086116 Text en Copyright © 2019 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Physical Sciences
Colizzi, Francesco
Perez-Gonzalez, Cibran
Fritzen, Remi
Levy, Yaakov
White, Malcolm F.
Penedo, J. Carlos
Bussi, Giovanni
Asymmetric base-pair opening drives helicase unwinding dynamics
title Asymmetric base-pair opening drives helicase unwinding dynamics
title_full Asymmetric base-pair opening drives helicase unwinding dynamics
title_fullStr Asymmetric base-pair opening drives helicase unwinding dynamics
title_full_unstemmed Asymmetric base-pair opening drives helicase unwinding dynamics
title_short Asymmetric base-pair opening drives helicase unwinding dynamics
title_sort asymmetric base-pair opening drives helicase unwinding dynamics
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842596/
https://www.ncbi.nlm.nih.gov/pubmed/31628254
http://dx.doi.org/10.1073/pnas.1901086116
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