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  Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters

Endres, T., Solvie, D., Heidelberger, J. B., Andriolett, V., Baluapuri, A., Ade, C. P., et al. (2021). Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters. Molecular Cell, In Press. doi:10.1016/j.molcel.2020.12.035.

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Endres, T., Author
Solvie, D., Author
Heidelberger, J. B., Author
Andriolett, V., Author
Baluapuri, A., Author
Ade, C. P., Author
Muhar, M., Author
Eilers, U., Author
Vos, S. M.1, Author              
Cramer, P.1, Author              
Zuber, J., Author
Beli, P., Author
Popov, N., Author
Wolf, E., Author
Gallant, P., Author
Eilers, M., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: MYC; HUWE1; PAF1c; RNAPII; double-strand break repair; histone H2B; ubiquitylation; E3 ligase
 Abstract: 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.

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Language(s): eng - English
 Dates: 2021-01-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2020.12.035
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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: In Press Start / End Page: - Identifier: -