Abstract：
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Dulin D,Vilfan ID,Berghuis BA,Hage S,Bamford DH,Poranen MM,Depken M,Dekker NHdoi
10.1016/j.celrep.2015.01.031subject
Has Abstractpub_date
2015-02-17 00:00:00pages
983-992issue
6issn
2211-1247pii
S2211-1247(15)00056-Xjournal_volume
10pub_type
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