PXD036674-1

PXD036674 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 06:45:01	ID requested
⏵ 1	2022-10-27 10:00:25	announced

Dataset with its publication pending

submitter keyword: BRCA1, DSBs, RNAPII,MYC, replication fork, FANCD2, multimerization, antisense transcription, HUWE1

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD036674

PRIDE project URI

• PRIDE
  1. PXD036674
     1. Label: PRIDE project
     2. Name: MYC multimers shield stalled replication forks from RNA polymerase