Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters
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EMS129538.pdf
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Accepted version
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Author(s)
Endres, Theresa
Solvie, Daniel
Heidelberger, Jan B
Andrioletti, Valentina
Baluapuri, Apoorva
Ade, Carsten P
Muhar, Matthias
Eilers, Ursula
Vos, Seychelle M
Cramer, Patrick
Date Issued
2021
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Endres, Theresa, Solvie, Daniel, Heidelberger, Jan B, Andrioletti, Valentina, Baluapuri, Apoorva et al. 2021. "Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters." Molecular Cell, 81 (4).
Version
Author's final manuscript
Abstract
© 2020 Elsevier Inc. The MYC oncoprotein globally affects the function of RNA polymerase II (RNAPII). The ability of MYC to promote transcription elongation depends on its ubiquitylation. Here, we show that MYC and PAF1c (polymerase II-associated factor 1 complex) interact directly and mutually enhance each other's association with active promoters. PAF1c is rapidly transferred from MYC onto RNAPII. This transfer is driven by the HUWE1 ubiquitin ligase and is required for MYC-dependent transcription elongation. MYC and HUWE1 promote histone H2B ubiquitylation, which alters chromatin structure both for transcription elongation and double-strand break repair. Consistently, MYC suppresses double-strand break accumulation in active genes in a strictly PAF1c-dependent manner. Depletion of PAF1c causes transcription-dependent accumulation of double-strand breaks, despite widespread repair-associated DNA synthesis. Our data show that the transfer of PAF1c from MYC onto RNAPII efficiently couples transcription elongation with double-strand break repair to maintain the genomic integrity of MYC-driven tumor cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2020.12.035
