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PXD036674-1

PXD036674 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMYC multimers shield stalled replication forks from RNA polymerase
DescriptionOncoproteins 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.
HostingRepositoryPRIDE
AnnounceDate2022-10-27
AnnouncementXMLSubmission_2022-10-27_10:00:25.249.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPetraBeli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-12 06:45:01ID requested
12022-10-27 10:00:25announced
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 affiliationInstitute of Molecular Biology, Ackermannweg 4, 55128 Mainz
contact emailp.beli@imb-mainz.de
lab head
PetraBeli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
dataset submitter
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Dataset FTP location
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