Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90242%2F23%3A00133755" target="_blank" >RIV/00216224:90242/23:00133755 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.celrep.2022.111901" target="_blank" >10.1016/j.celrep.2022.111901</a>
Alternative languages
Result language
angličtina
Original language name
Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106
Original language description
The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be compet-itively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase. This shows that the entire product-template duplex backtracks by 5 nt, bringing the singly incorporated T1106 to the +1 position, where it forms an unexpected T1106:U wobble base pair. Similar structures show that influ-enza B polymerase also backtracks after consecutive T1106 incorporation, regardless of whether prior single incorporation has occurred. These results give insight into the unusual mechanism of chain termination by pyr-azinecarboxamide base analogs. Consecutive incorporation destabilizes the proximal end of the product -template duplex, promoting irreversible backtracking to a more energetically favorable overall configuration.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
—
Continuities
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Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Reports
ISSN
2211-1247
e-ISSN
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Volume of the periodical
42
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
24
Pages from-to
1-24
UT code for WoS article
000964718900001
EID of the result in the Scopus database
2-s2.0-85147311380