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dc.contributor.authorYuzenkova, Yuliaen_US
dc.contributor.authorBochkareva, Aleksandraen_US
dc.contributor.authorTadigotla, Vasisht R.en_US
dc.contributor.authorRoghanian, Mohammaden_US
dc.contributor.authorZorov, Savvaen_US
dc.contributor.authorSeverinov, Konstantinen_US
dc.contributor.authorZenkin, Nikolayen_US
dc.date.accessioned2012-01-12T16:41:19Z
dc.date.available2012-01-12T16:41:19Z
dc.date.copyright2010
dc.date.issued2010-5-7
dc.identifier.citationYuzenkova, Yulia, Aleksandra Bochkareva, Vasisht R Tadigotla, Mohammad Roghanian, Savva Zorov, Konstantin Severinov, Nikolay Zenkin. "Stepwise mechanism for transcription fidelity" BMC Biology 8:54. (2010)
dc.identifier.issn1741-7007
dc.identifier.urihttps://hdl.handle.net/2144/3355
dc.description.abstractBACKGROUND. Transcription is the first step of gene expression and is characterized by a high fidelity of RNA synthesis. During transcription, the RNA polymerase active centre discriminates against not just non-complementary ribo NTP substrates but also against complementary 2'- and 3'-deoxy NTPs. A flexible domain of the RNA polymerase active centre, the Trigger Loop, was shown to play an important role in this process, but the mechanisms of this participation remained elusive. RESULTS. Here we show that transcription fidelity is achieved through a multi-step process. The initial binding in the active centre is the major discrimination step for some non-complementary substrates, although for the rest of misincorporation events discrimination at this step is very poor. During the second step, non-complementary and 2'-deoxy NTPs are discriminated against based on differences in reaction transition state stabilization and partly in general base catalysis, for correct versus non-correct substrates. This step is determined by two residues of the Trigger Loop that participate in catalysis. In the following step, non-complementary and 2'-deoxy NTPs are actively removed from the active centre through a rearrangement of the Trigger Loop. The only step of discrimination against 3'-deoxy substrates, distinct from the ones above, is based on failure to orient the Trigger Loop catalytic residues in the absence of 3'OH. CONCLUSIONS. We demonstrate that fidelity of transcription by multi-subunit RNA polymerases is achieved through a stepwise process. We show that individual steps contribute differently to discrimination against various erroneous substrates. We define the mechanisms and contributions of each of these steps to the overall fidelity of transcription.en_US
dc.description.sponsorshipNational Institutes of Health (GM64530); Biotechnology and Biological Sciences Research Council (BB/F006462/1, BB/I004564/1); European Research Council (ERC-2007-StG 202994-MTP)en_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2010 Yuzenkova et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleStepwise Mechanism for Transcription Fidelityen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1741-7007-8-54
dc.identifier.pmid20459653
dc.identifier.pmcid2874521


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Copyright 2010 Yuzenkova et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2010 Yuzenkova et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.