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Content archived on 2024-05-27

Mechanisms of Transcription Proofreading

Objective

Transcription, the copying of DNA into RNA, is the first step in the realisation of genetic information. RNA is either directly used by the cell or decoded into proteins during translation. The accuracy of transcription is thus essential for proper functioning of the cell. In all living organisms transcription is performed by multisubunit RNA polymerases, enzymes that are highly conserved in evolution from bacteria to humans. Surprisingly, the mechanisms that ensure accuracy of transcription remain largely unknown. Recently I discovered a novel mechanism of transcriptional proofreading used by bacterial RNA polymerase. I showed that the RNA transcript itself assists RNA polymerase in identifying and correcting mistakes. This discovery led to the hypothesis that this transcript-assisted proofreading is the universal mechanism of transcriptional error correction in all three domains of life. In this proposal we will investigate this hypothesis and search for other mechanisms of transcriptional proofreading used by bacterial, archaeal, and three eukaryotic RNA polymerases. For the first time experimental systems will be built for the simultaneous investigation of transcription elongation complexes formed by bacterial, archaeal and eukaryotic RNA polymerases I, II and III, which will be used to elucidate the mechanisms of error correction used by these RNA polymerases. Using molecular modelling, directed mutagenesis and in vivo screenings we will investigate the impact of these proofreading mechanisms on the total fidelity of transcription in vitro and in vivo. Experimental systems built in this research may be of use for screening of potential antibacterial and antifungal drugs taking advantage of the simultaneous investigation of RNA polymerases from all domains of Life. This research may also have potential applications in drug design by providing new targets for antibiotics.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2007-StG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITY OF NEWCASTLE UPON TYNE
EU contribution
€ 1 149 831,00
Address
KINGS GATE
NE1 7RU Newcastle Upon Tyne
United Kingdom

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Region
North East (England) Northumberland and Tyne and Wear Tyneside
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)

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