KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH, Valentina SPERANZINI, Alex PFLUG, Johanna HUCHTING, Chris MEIER, De Vivo MARCO a Stephen CUSACK. Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106. Cell Reports. CAMBRIDGE: Cell Press, 2023, roč. 42, č. 1, s. 1-24. ISSN 2211-1247. Dostupné z: https://dx.doi.org/10.1016/j.celrep.2022.111901. |
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@article{2383037, author = {Kouba, Tomas and Dubankova, Anna and Drncova, Petra and Donati, Elisa and Vidossich, Pietro and Speranzini, Valentina and Pflug, Alex and Huchting, Johanna and Meier, Chris and Marco, De Vivo and Cusack, Stephen}, article_location = {CAMBRIDGE}, article_number = {1}, doi = {http://dx.doi.org/10.1016/j.celrep.2022.111901}, keywords = {T-705 FAVIPIRAVIR; TRANSCRIPTION; RNA polymerase; REPLICATION; INFECTIONS; CryoEM; pyr-azinecarboxamide base analogs}, language = {eng}, issn = {2211-1247}, journal = {Cell Reports}, title = {Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106}, url = {https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub}, volume = {42}, year = {2023} }
TY - JOUR ID - 2383037 AU - Kouba, Tomas - Dubankova, Anna - Drncova, Petra - Donati, Elisa - Vidossich, Pietro - Speranzini, Valentina - Pflug, Alex - Huchting, Johanna - Meier, Chris - Marco, De Vivo - Cusack, Stephen PY - 2023 TI - Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106 JF - Cell Reports VL - 42 IS - 1 SP - 1-24 EP - 1-24 PB - Cell Press SN - 22111247 KW - T-705 FAVIPIRAVIR KW - TRANSCRIPTION KW - RNA polymerase KW - REPLICATION KW - INFECTIONS KW - CryoEM KW - pyr-azinecarboxamide base analogs UR - https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub N2 - 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. ER -
KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH, Valentina SPERANZINI, Alex PFLUG, Johanna HUCHTING, Chris MEIER, De Vivo MARCO a Stephen CUSACK. Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106. \textit{Cell Reports}. CAMBRIDGE: Cell Press, 2023, roč.~42, č.~1, s.~1-24. ISSN~2211-1247. Dostupné z: https://dx.doi.org/10.1016/j.celrep.2022.111901.
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