PXD019923

PXD019923 is an original dataset announced via ProteomeXchange.

Title	USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks
Description	DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with DNA metabolic processes such as replication, transcription, and recombination. SPRTN is a replication-coupled DNA-dependent metalloprotease that degrades proteins crosslinked to DNA to promote DPC repair. SPRTN function is tightly regulated by a monoubiquitin switch that controls SPRTN chromatin accessibility during DPC repair. The deubiquitinase regulating SPRTN function in DPC repair is unknown. To identify SPRTN modifiers, we performed tandem-affinity purification and mass spectrometry (TAP-MS) analysis of SFB (S-FLAG-streptavidin binding peptide)-tagged SPRTN expressed in HEK 293T cells. We screened the MS list for proteins that are known to function as a deubiquitinase and identified only one potential SPRTN modifier, USP11 deubiquitinase. A reciprocal TAP-MS analysis of SFB-USP11 expressed in HEK 293T cells treated with camptothecin (CPT) immunoprecipitated SPRTN. USP11 interacts with SPRTN and cleaves monoubiquitinated SPRTN in cells and in vitro. USP11 depletion impaired SPRTN deubiquitination in response to formaldehyde-induced DPCs. Loss of USP11 causes an accumulation of unrepaired DPCs and cellular hypersensitivity to treatment with DPC-inducing agents. Our findings elucidates the function of USP11 in the regulation of SPRTN monoubiquitination and SPRTN-mediated DPC repair.
HostingRepository	PRIDE
AnnounceDate	2021-04-01
AnnouncementXML	Submission_2021-04-01_11:06:32.088.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gargi Ghosal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-21 23:39:50	ID requested
⏵ 1	2021-04-01 11:06:32	announced

Perry M, Biegert M, Kollala SS, Mallard H, Su G, Kodavati M, Kreiling N, Holbrook A, Ghosal G, USP11 mediates repair of DNA-protein cross-links by deubiquitinating SPRTN metalloprotease. J Biol Chem, 296():100396(2021) [pubmed]

submitter keyword: DPC, DPC repair, Top1-ccs, SPRTN, monoubiquitinated SPRTN, deubiquitination, USP11

Gargi Ghosal
contact affiliation	Genetics, Cell Biology and Anatomy; University of Nebraska Medical Center; USA
contact email	gargi.ghosal@unmc.edu
lab head
Gargi Ghosal
contact affiliation	University of Nebraska Medical Center
contact email	gargi.ghosal@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019923
     1. Label: PRIDE project
     2. Name: USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks