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| Title | Translation selectively destroys non-functional transcription complexes. |
|---|---|
| Journal, issue, pages | Nature, Vol. 626, Issue 8000, Page 891-896, Year 2024 |
| Publish date | Feb 7, 2024 |
 Authors | Jason Woodgate / Hamed Mosaei / Pavel Brazda / Flint Stevenson-Jones / Nikolay Zenkin /  |
| PubMed Abstract | Transcription elongation stalls at lesions in the DNA template. For the DNA lesion to be repaired, the stalled transcription elongation complex (EC) has to be removed from the damaged site. Here we ...Transcription elongation stalls at lesions in the DNA template. For the DNA lesion to be repaired, the stalled transcription elongation complex (EC) has to be removed from the damaged site. Here we show that translation, which is coupled to transcription in bacteria, actively dislodges stalled ECs from the damaged DNA template. By contrast, paused, but otherwise elongation-competent, ECs are not dislodged by the ribosome. Instead, they are helped back into processive elongation. We also show that the ribosome slows down when approaching paused, but not stalled, ECs. Our results indicate that coupled ribosomes functionally and kinetically discriminate between paused ECs and stalled ECs, ensuring the selective destruction of only the latter. This functional discrimination is controlled by the RNA polymerase's catalytic domain, the Trigger Loop. We show that the transcription-coupled DNA repair helicase UvrD, proposed to cause backtracking of stalled ECs, does not interfere with ribosome-mediated dislodging. By contrast, the transcription-coupled DNA repair translocase Mfd acts synergistically with translation, and dislodges stalled ECs that were not destroyed by the ribosome. We also show that a coupled ribosome efficiently destroys misincorporated ECs that can cause conflicts with replication. We propose that coupling to translation is an ancient and one of the main mechanisms of clearing non-functional ECs from the genome. |
 External links | Nature / PubMed:38326611 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.87 Å |
| Structure data | EMDB-17586, PDB-8pbl: |
| Chemicals |  ChemComp-ZN:  ChemComp-MG: |
| Source |
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 Keywords | TRANSCRIPTION / RNA Polymerase / RNAP / Gene Expression / DNA lesion / Stalling |
escherichia coli (E. coli)