Proteomics

Dataset Information

0

SPARTAN Protease and Checkpoint Kinase 1 Cross-Activation Loop Safeguards Genome Stability

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: iolanda Vendrell  

LAB HEAD: Kristijan Ramadan

PROVIDER: PXD006741 | Pride | 2019-11-08

REPOSITORIES: Pride

Json Xml
altmetric image

Publications

The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient in SPRTN protease exhibit DPC-induced replication stress and genome instability, manifesting as premature ageing and liver cancer. Here, we provide a body of evidence suggesting that SPRTN activates the ATR-CHK1 phosphorylation signalling cascade during physiological DNA replication by proteolysis-dependent eviction of CHK1 from replicative chromatin. During this  ...[more]

Similar Datasets

Proteomics Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Removal
2017-03-29 | MSV000080743 | MassIVE
Proteomics Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Removal
2016-10-06 | PXD004154 | Pride
Proteomics DNA replication regulates SPRTN- and Proteasome-dependent DPC proteolysis
2019-02-13 | PXD008831 | Pride
Proteomics USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks
2021-04-01 | PXD019923 | Pride
Proteomics Transcription-coupled DNA-Protein Crosslink repair by CSB and CRL4(CSA)-mediated degradation
2024-02-09 | PXD041679 | Pride
Proteomics Mechanism and function of DNA replication-independent DNA-protein crosslink repair via the SUMO pathway
2021-08-06 | PXD021947 | Pride
Proteomics,Multiomics A SUMO-mediated protective response to DNA-protein crosslinks
2019-03-26 | PXD009040 | Pride
Proteomics TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts
2020-03-13 | PXD017239 | Pride
Proteomics The Aspartic Protease Ddi1 Contributes to DNA-Protein Crosslink Repair in Yeast
2019-11-22 | PXD016376 | Pride
Genomics The cullin Rtt101 promotes ubiquitin-dependent DNA-Protein Crosslink repair across the cell cycle
2023-11-10 | GSE247492 | GEO