A DNA-centered explanation of the DNA polymerase translocation mechanism

Abstract DNA polymerase couples chemical energy to translocation along a DNA template with a specific directionality while it replicates genetic information. According to single-molecule manipulation experiments, the polymerase-DNA complex can work against loads greater than 50 pN. It is not known,...

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Autor principal:	J. Ricardo Arias-Gonzalez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b4823d6a736049069ae21af33324cfae
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spelling	oai:doaj.org-article:b4823d6a736049069ae21af33324cfae2021-12-02T16:06:36ZA DNA-centered explanation of the DNA polymerase translocation mechanism10.1038/s41598-017-08038-22045-2322https://doaj.org/article/b4823d6a736049069ae21af33324cfae2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08038-2https://doaj.org/toc/2045-2322Abstract DNA polymerase couples chemical energy to translocation along a DNA template with a specific directionality while it replicates genetic information. According to single-molecule manipulation experiments, the polymerase-DNA complex can work against loads greater than 50 pN. It is not known, on the one hand, how chemical energy is transduced into mechanical motion, accounting for such large forces on sub-nanometer steps, and, on the other hand, how energy consumption in fidelity maintenance integrates in this non-equilibrium cycle. Here, we propose a translocation mechanism that points to the flexibility of the DNA, including its overstretching transition, as the principal responsible for the DNA polymerase ratcheting motion. By using thermodynamic analyses, we then find that an external load hardly affects the fidelity of the copying process and, consequently, that translocation and fidelity maintenance are loosely coupled processes. The proposed translocation mechanism is compatible with single-molecule experiments, structural data and stereochemical details of the DNA-protein complex that is formed during replication, and may be extended to RNA transcription.J. Ricardo Arias-GonzalezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. Ricardo Arias-Gonzalez A DNA-centered explanation of the DNA polymerase translocation mechanism
description	Abstract DNA polymerase couples chemical energy to translocation along a DNA template with a specific directionality while it replicates genetic information. According to single-molecule manipulation experiments, the polymerase-DNA complex can work against loads greater than 50 pN. It is not known, on the one hand, how chemical energy is transduced into mechanical motion, accounting for such large forces on sub-nanometer steps, and, on the other hand, how energy consumption in fidelity maintenance integrates in this non-equilibrium cycle. Here, we propose a translocation mechanism that points to the flexibility of the DNA, including its overstretching transition, as the principal responsible for the DNA polymerase ratcheting motion. By using thermodynamic analyses, we then find that an external load hardly affects the fidelity of the copying process and, consequently, that translocation and fidelity maintenance are loosely coupled processes. The proposed translocation mechanism is compatible with single-molecule experiments, structural data and stereochemical details of the DNA-protein complex that is formed during replication, and may be extended to RNA transcription.
format	article
author	J. Ricardo Arias-Gonzalez
author_facet	J. Ricardo Arias-Gonzalez
author_sort	J. Ricardo Arias-Gonzalez
title	A DNA-centered explanation of the DNA polymerase translocation mechanism
title_short	A DNA-centered explanation of the DNA polymerase translocation mechanism
title_full	A DNA-centered explanation of the DNA polymerase translocation mechanism
title_fullStr	A DNA-centered explanation of the DNA polymerase translocation mechanism
title_full_unstemmed	A DNA-centered explanation of the DNA polymerase translocation mechanism
title_sort	dna-centered explanation of the dna polymerase translocation mechanism
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b4823d6a736049069ae21af33324cfae
work_keys_str_mv	AT jricardoariasgonzalez adnacenteredexplanationofthednapolymerasetranslocationmechanism AT jricardoariasgonzalez dnacenteredexplanationofthednapolymerasetranslocationmechanism
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A DNA-centered explanation of the DNA polymerase translocation mechanism

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