PXD011850 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2019-03-25 |
AnnouncementXML | Submission_2019-03-25_07:14:47.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 |
Dataset History
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. |
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] |
Keyword List
submitter keyword: MDC1 TOPBP1 Mitosis |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011850
- Label: PRIDE project
- Name: MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis