PXD006741 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | SPARTAN Protease and Checkpoint Kinase 1 Cross-Activation Loop Safeguards Genome Stability |
Description | DNA-protein crosslinks (DPCs) are abundant DNA lesions, which constantly challenge genome stability by interfering with DNA replication. SPARTAN (SPRTN) protease plays a central role in DPCs repair in proliferative vertebrate cells. SPRTN is a constitutive part of the DNA replication machinery and its protease activity is essential for DNA replication fork progression. How this essential protease is activated and regulated during DNA replication is not known. By using biochemical, cell biological and genetic approaches in human cell lines and Zebrafish model system, we identified that SPRTN cleaves covalently crosslinked Checkpoint kinase 1 (CHK1) from chromatin and releases CHK1 during physiological DNA replication. Proteolysed CHK1 is activated and in turn phosphorylates SPRTN. Phosphorylated SPRTN is further recruited to chromatin to proteolyse DPCs that ensures unperturbed DNA replication. Our data suggest SPRTN-CHK1 cross-activation loop is essential for genome stability. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:38:49.435.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | iolanda Vendrell |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-06-19 01:54:06 | ID requested | |
1 | 2019-11-11 00:44:49 | announced | |
⏵ 2 | 2024-10-22 04:38:50 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41467-019-11095-y; |
Halder S, Torrecilla I, Burkhalter MD, Popovi, ć M, Fielden J, Vaz B, Oehler J, Pilger D, Lessel D, Wiseman K, Singh AN, Vendrell I, Fischer R, Philipp M, Ramadan K, SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication. Nat Commun, 10(1):3142(2019) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: cancer,SPARTAN protease, DNA-protein crosslinks, ageing, genome stability, CHK1 kinase, DNA replication |
Contact List
Kristijan Ramadan |
contact affiliation | CRUK and MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK |
contact email | kristijan.ramadan@oncology.ox.ac.uk |
lab head | |
iolanda Vendrell |
contact affiliation | CRUK-MRC Oxford Institute for Radiation Oncology, Oxford University |
contact email | iolanda.vendrell@oncology.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006741
- Label: PRIDE project
- Name: SPARTAN Protease and Checkpoint Kinase 1 Cross-Activation Loop Safeguards Genome Stability