PXD011850

PXD011850 is an original dataset announced via ProteomeXchange.

Title	MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis
Description	MDC1 is a large, modular phospho-protein scaffold that mediates recruitment of signaling and repair complexes to sites of DNA double-strand breaks (DSBs). MDC1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with phosphorylated H2AX (γH2AX), where it recruits downstream factors via direct phosphorylation-dependent protein-protein interactions. Here, using unbiased proteomic analyses we identify a highly conserved protein interaction surface near the MDC1 N-terminus for the DNA damage response protein TOPBP1. We show that TOPBP1 directly binds to two residues in MDC1 that are phosphorylated by CK2. Interestingly, we find that TOPBP1 recruitment to DSBs depends on direct interaction with MDC1 only during mitosis. Furthermore, we demonstrate that disrupting MDC1-TOPBP1 binding causes hypersensitivity to ionizing radiation in mitosis, as well as increased micronuclei and chromosomal instability. Thus, our results highlight an important and hitherto unnoticed function for MDC1 and TOPBP1 in maintaining genome stability during cell division.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:50:46.530.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-27 07:43:27	ID requested
1	2019-03-25 07:14:48	announced
⏵ 2	2024-10-22 04:50:52	announced	2024-10-22: Updated project metadata.

Leimbacher PA, Jones SE, Shorrocks AK, de Marco Zompit M, Day M, Blaauwendraad J, Bundschuh D, Bonham S, Fischer R, Fink D, Kessler BM, Oliver AW, Pearl LH, Blackford AN, Stucki M, MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis. Mol Cell, 74(3):571-583.e8(2019) [pubmed]

10.1016/j.molcel.2019.02.014;

submitter keyword: MDC1 TOPBP1 Mitosis

Roman Fischer
contact affiliation	Discovery Proteomics Facility University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
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/2019/03/PXD011850

PRIDE project URI

• PRIDE
  1. PXD011850
     1. Label: PRIDE project
     2. Name: MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis