Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path

In high fidelity DNA polymerases the exonuclease site is distal from the polymerization site and it is unknown how the primer strand travels between the two sites when mis-incorporated nucleotides must be removed. Here, the authors perform MD simulations and identify an optimal path for DNA primer s...

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Main Authors:	Thomas Dodd, Margherita Botto, Fabian Paul, Rafael Fernandez-Leiro, Meindert H. Lamers, Ivaylo Ivanov
Format:	Article
Language:	English
Published:	Nature Publishing Group 2020-10-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-020-19165-2

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spelling	doaj-ed53db85cf324dffb2be1a08c1015c862021-05-11T08:55:43ZengNature Publishing GroupNature Communications2041-17232020-10-0111111110.1038/s41467-020-19165-2Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined pathThomas Dodd0Margherita Botto1Fabian Paul2Rafael Fernandez-Leiro3Meindert H. Lamers4Ivaylo Ivanov5Department of Chemistry, Georgia State UniversityDepartment of Cell and Chemical Biology, Leiden University Medical CenterDepartment of Biochemistry & Molecular Biology, University of ChicagoSpanish National Cancer Research Centre (CNIO)Department of Cell and Chemical Biology, Leiden University Medical CenterDepartment of Chemistry, Georgia State UniversityIn high fidelity DNA polymerases the exonuclease site is distal from the polymerization site and it is unknown how the primer strand travels between the two sites when mis-incorporated nucleotides must be removed. Here, the authors perform MD simulations and identify an optimal path for DNA primer strand translocation in the E. coli replicative DNA polymerase III and characterise the kinetics and dynamics of the Pol III pol-to-exo mode transition, which is validated with mutagenesis experiments.https://doi.org/10.1038/s41467-020-19165-2
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Thomas Dodd Margherita Botto Fabian Paul Rafael Fernandez-Leiro Meindert H. Lamers Ivaylo Ivanov
spellingShingle	Thomas Dodd Margherita Botto Fabian Paul Rafael Fernandez-Leiro Meindert H. Lamers Ivaylo Ivanov Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path Nature Communications
author_facet	Thomas Dodd Margherita Botto Fabian Paul Rafael Fernandez-Leiro Meindert H. Lamers Ivaylo Ivanov
author_sort	Thomas Dodd
title	Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path
title_short	Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path
title_full	Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path
title_fullStr	Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path
title_full_unstemmed	Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path
title_sort	polymerization and editing modes of a high-fidelity dna polymerase are linked by a well-defined path
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2020-10-01
description	In high fidelity DNA polymerases the exonuclease site is distal from the polymerization site and it is unknown how the primer strand travels between the two sites when mis-incorporated nucleotides must be removed. Here, the authors perform MD simulations and identify an optimal path for DNA primer strand translocation in the E. coli replicative DNA polymerase III and characterise the kinetics and dynamics of the Pol III pol-to-exo mode transition, which is validated with mutagenesis experiments.
url	https://doi.org/10.1038/s41467-020-19165-2
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Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path

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