PXD023242

PXD023242 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin-dependent transfer of PAF1c from MYC onto RNA Polymerase controls double-strand break repair at active promoters
Description	MYC family proteins are oncogenic transcription factors that can globally affect the function of RNA Polymerase II (RNAPII). The ability of MYC proteins to promote transcription elongation depends on their ubiquitination, but the underlying mechanism and its biological relevance are unknown. Here we show that MYC and the Polymerase II associated factor, PAF1c, interact directly and their function is mutually dependent, since the specific binding of MYC to active promoters depends on PAF1c and, conversely, PAF1c is required for MYC-dependent pause release. Upon binding, PAF1c is rapidly transferred from MYC onto RNAPII and this transfer is driven by the HUWE1 ubiquitin ligase. Both MYC and HUWE1 globally control histone H2B ubiquitylation, which promotes transcriptional elongation and alters chromatin structure for double-strand break repair. Consistently, MYC suppresses the accumulation of double-strand breaks at promoters in response to topoisomerase II inhibition. While depletion of PAF1c has only minor effects on MYC-dependent gene expression, MYC induces rampant transcription-dependent DNA damage in PAF1c-depleted cells. We propose that the HUWE1-dependent transfer of PAF1c from MYC onto RNAPII is critical for absorbing the topological stress accompanied with deregulated and oncogenic transcription.
HostingRepository	PRIDE
AnnounceDate	2021-02-15
AnnouncementXML	Submission_2021-02-15_07:43:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-21 02:37:31	ID requested
⏵ 1	2021-02-15 07:43:39	announced

Dataset with its publication pending

submitter keyword: MYC, HUWE1, PAF1c, RNAPII, DNA repair

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023242
     1. Label: PRIDE project
     2. Name: Ubiquitin-dependent transfer of PAF1c from MYC onto RNA Polymerase controls double-strand break repair at active promoters