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  Structural basis of mitochondrial transcription initiation.

Hillen, H. S., Morozov, Y. I., Sarfallah, A., Temiakov, D., & Cramer, P. (2017). Structural basis of mitochondrial transcription initiation. Cell, 171(5), 1072-1081. doi:10.1016/j.cell.2017.10.036.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-34AC-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-2752-7
Genre: Journal Article

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2503453.pdf (Publisher version), 10MB
 
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 Creators:
Hillen, H. S.1, Author              
Morozov, Y. I., Author
Sarfallah, A., Author
Temiakov, D., Author
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: Mitochondria; Transcription; POLRMT; TFAM; TFB2M; TEFM; Initiation; Polymerase; Initiation Complex
 Abstract: Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.

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Language(s): eng - English
 Dates: 2017-11-162017-11-16
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cell.2017.10.036
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 171 (5) Sequence Number: - Start / End Page: 1072 - 1081 Identifier: -