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

Authors :
Endres T
Solvie D
Heidelberger JB
Andrioletti V
Baluapuri A
Ade CP
Muhar M
Eilers U
Vos SM
Cramer P
Zuber J
Beli P
Popov N
Wolf E
Gallant P
Eilers M
Source :
Molecular cell [Mol Cell] 2021 Feb 18; Vol. 81 (4), pp. 830-844.e13. Date of Electronic Publication: 2021 Jan 15.
Publication Year :
2021

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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4164
Volume :
81
Issue :
4
Database :
MEDLINE
Journal :
Molecular cell
Publication Type :
Academic Journal
Accession number :
33453168
Full Text :
https://doi.org/10.1016/j.molcel.2020.12.035