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  Structural basis of Integrator-mediated transcription regulation

Fianu, I., Chen, Y., Dienemann, C., Dybkov, O., Linden, A., Urlaub, H., et al. (2021). Structural basis of Integrator-mediated transcription regulation. Science, 374(6569), 883-887. doi:10.1126/science.abk0154.

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 Creators:
Fianu, I.1, Author              
Chen, Y.1, Author              
Dienemann, C.1, Author              
Dybkov, O.2, Author              
Linden, A.3, Author              
Urlaub, H.4, Author              
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              
2Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              
3Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
4Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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 Abstract: Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.

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Language(s): eng - English
 Dates: 2021-11-112021-11-12
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1126/science.abk0154
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Title: Science
Source Genre: Journal
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Pages: - Volume / Issue: 374 (6569) Sequence Number: - Start / End Page: 883 - 887 Identifier: -