PXD006741

PXD006741 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: cancer,SPARTAN protease, DNA-protein crosslinks, ageing, genome stability, CHK1 kinase, DNA replication

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

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/2019/11/PXD006741

PRIDE project URI

• PRIDE
  1. PXD006741
     1. Label: PRIDE project
     2. Name: SPARTAN Protease and Checkpoint Kinase 1 Cross-Activation Loop Safeguards Genome Stability