PXD036674 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | MYC multimers shield stalled replication forks from RNA polymerase |
Description | Oncoproteins of the MYC family drive the development of numerous human tumors. In unperturbed cells, MYC proteins bind to virtually all active promoters and control transcription by RNA Polymerase II (RNAPII). MYC proteins can also coordinate transcription with DNA replication and promote the repair of transcription-associated DNA damage, but how they exert these mechanistically diverse functions is unknown. Here we show that MYC dissociates from many of its binding sites in active promoters and forms multimeric, often sphere-like structures in response to perturbation of transcription elongation, mRNA splicing or inhibition of the proteasome. Multimerization is accompanied by a global change in the MYC interactome towards proteins involved in transcription termination and RNA processing. MYC multimers accumulate on chromatin immediately adjacent to stalled replication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks. MYC multimerization is triggered in a HUWE1- and ubiquitylation-dependent manner. At active promoters, MYC multimers block antisense transcription and stabilize FANCD2 association with chromatin. This limits DNA double-strand break formation during S phase, suggesting that multimerization of MYC enables tumor cells to proliferate under stressful conditions. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-27 |
AnnouncementXML | Submission_2022-10-27_10:00:25.249.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | PetraBeli |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-12 06:45:01 | ID requested | |
⏵ 1 | 2022-10-27 10:00:25 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: BRCA1, DSBs, RNAPII,MYC, replication fork, FANCD2, multimerization, antisense transcription, HUWE1 |
Contact List
PetraBeli |
contact affiliation | Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz |
contact email | p.beli@imb-mainz.de |
lab head | |
PetraBeli |
contact affiliation | Institute of Molecular Biology (IMB), Mainz, Germany |
contact email | p.beli@imb-mainz.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036674
- Label: PRIDE project
- Name: MYC multimers shield stalled replication forks from RNA polymerase