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PXD011850

PXD011850 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis
DescriptionMDC1 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:50:46.530.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRoman Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-11-27 07:43:27ID requested
12019-03-25 07:14:48announced
22024-10-22 04:50:52announced2024-10-22: Updated project metadata.
Publication List
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;
Keyword List
submitter keyword: MDC1 TOPBP1 Mitosis
Contact List
Roman Fischer
contact affiliationDiscovery Proteomics Facility University of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliationUniversity of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
dataset submitter
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Dataset FTP location
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Repository Record List
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