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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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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. |
format | Online Article Text |
id | pubmed-6842596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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