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Exploring and predicting DNA template dependent variation in transcription
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Reliable transmission of information from DNA to proteins is a pre-requisite for all life, where substitution errors in the polypeptide chain may arise from transcription, aminoacylation of tRNAs or translation. The fidelity control mechanisms in transcription have nevertheless received little attention, based on the assumption that the transcriptional error is masked by the translational error. This thesis shows how accuracy theory can be applied to transcription to elucidate the principles of transcriptional accuracy. The DNA template dependent transcriptional accuracy variation is studied through modelling based on transition state theory, using thermodynamic properties of the nucleic acids in the transcription bubble. The models show that the error frequency variation in transcription causes it to surpass the translational error in some sequence contexts, making transcription a significant source of amino acids substitution errors.

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2012. , 17 p.
Keyword [en]
transcription, accuracy, kinetic proofreading, selection
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Molecular Biotechnology
Identifiers
URN: urn:nbn:se:uu:diva-181004OAI: oai:DiVA.org:uu-181004DiVA: diva2:552631
Presentation
2012-09-28, C8:301, Uppsala Biomedicinska Centrum (BMC), Husarg. 3, Uppsala, 14:52 (English)
Opponent
Supervisors
Funder
Vinnova
Available from: 2012-10-02 Created: 2012-09-14 Last updated: 2012-10-02Bibliographically approved
List of papers
1. Large DNA Template Dependent Error Variation During Transcription
Open this publication in new window or tab >>Large DNA Template Dependent Error Variation During Transcription
2014 (English)In: Biophysics and Structure to Counter Threats and Challenges / [ed] Joseph D. Puglisi, Manolia V. Margaris, Springer Netherlands, 2014, , 19 p.39-57 p.Chapter in book (Other academic)
Abstract [en]

The accuracy of an enzymatic reaction system is the propensity toprocess the correct, or cognate, substrate over similar, non-cognate substrates. Thisis of particular importance to polymerization reactions with a template sequence,like transcription, translation and replication. A theoretical framework for theanalysis of accuracy control is presented, including initial substrate selection andkinetic proofreading. This framework allows for analysis not only of the efficiencyof accuracy control, but also its source in standard free energy differences andequilibrium constants and its relation to the rate of product formation. A key featureis the separation of the selection in a context dependent discard parameter anda context independent discrimination parameter. When the theory is applied tothe example of prokaryote transcription, it is shown that the discard parameter,composed by experimentally well-defined values, induces a large template sequencedependent error rate variation.

Place, publisher, year, edition, pages
Springer Netherlands, 2014. 19 p.
Series
NATO Science for Peace and Security Series B: Physics and Biophysics, ISSN 1874-6500
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Molecular Biotechnology
Identifiers
urn:nbn:se:uu:diva-181002 (URN)10.1007/978-94-007-4923-8_3 (DOI)978-94-007-4922-1 (ISBN)
Conference
Biophysics and Structure to Counter Threats and Challenges
Funder
VINNOVA
Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2015-10-20
2. Large transcriptional accuracy variation advocate transcription as a source of amino acid sequence errors
Open this publication in new window or tab >>Large transcriptional accuracy variation advocate transcription as a source of amino acid sequence errors
(English)Manuscript (preprint) (Other academic)
National Category
Biochemistry and Molecular Biology
Research subject
Biology with specialization in Molecular Biotechnology
Identifiers
urn:nbn:se:uu:diva-181003 (URN)
Funder
Vinnova
Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2012-10-02

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