Elongation-Competent Pauses Govern the Fidelity of a Viral RNA-Dependent RNA Polymerase.

Autor:	Dulin D; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands., Vilfan ID; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands., Berghuis BA; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands., Hage S; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands., Bamford DH; Department of Biosciences, University of Helsinki, Viikki Biocenter 2, P.O. Box 56 (Viikinkaari 5), 00014 Helsinki, Finland; Institute of Biotechnology, University of Helsinki, Viikki Biocenter 2, P.O. Box 56 (Viikinkaari 5), 00014 Helsinki, Finland., Poranen MM; Department of Biosciences, University of Helsinki, Viikki Biocenter 2, P.O. Box 56 (Viikinkaari 5), 00014 Helsinki, Finland. Electronic address: minna.poranen@helsinki.fi., Depken M; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands. Electronic address: s.m.depken@tudelft.nl., Dekker NH; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands. Electronic address: n.h.dekker@tudelft.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Feb 17; Vol. 10 (6), pp. 983-992. Date of Electronic Publication: 2015 Feb 12.
DOI:	10.1016/j.celrep.2015.01.031
Abstrakt:	RNA viruses have specific mutation rates that balance the conflicting needs of an evolutionary response to host antiviral defenses and avoidance of the error catastrophe. While most mutations are known to originate in replication errors, difficulties of capturing the underlying dynamics have left the mechanochemical basis of viral mutagenesis unresolved. Here, we use multiplexed magnetic tweezers to investigate error incorporation by the bacteriophage Φ6 RNA-dependent RNA polymerase. We extract large datasets fingerprinting real-time polymerase dynamics over four magnitudes in time, in the presence of nucleotide analogs, and under varying NTP and divalent cation concentrations and fork stability. Quantitative analysis reveals a new pause state that modulates polymerase fidelity and so ties viral polymerase pausing to the biological function of optimizing virulence. Adjusting the frequency of such pauses offers a target for therapeutics and may also reflect an evolutionary strategy for virus populations to track the gradual evolution of their hosts. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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