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PXD045154-2

PXD045154 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInterferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15
DescriptionDNA replication and repair defects or genotoxic treatments trigger interferon (IFN)-mediated inflammatory responses. However, whether and how IFN signaling in turn impacts the DNA replication process has remained elusive. Here we show that basal levels of the IFN-stimulated gene 15, ISG15, and its conjugation (ISGylation) are essential to protect nascent DNA from degradation. Moreover, IFN treatment restores replication fork stability in BRCA1/2-deficient cells, which strictly depends on topoisomerase-1, and rescues lethality of BRCA2-deficient mouse embryonic stem cells. Although IFN activates hundreds of genes, these effects are specifically mediated by ISG15 and ISGylation, as their inactivation suppresses the impact of IFN on DNA replication. ISG15 depletion significantly reduces cell proliferation rates in human BRCA1-mutated triple-negative, whereas its upregulation results in increased resistance to the chemotherapeutic drug cisplatin in mouse BRCA2-deficient breast cancer cells, respectively. Accordingly, cells carrying BRCA1/2 defects consistently show increased ISG15 levels, which we propose as a novel, in-built mechanism of drug resistance linked to BRCAness.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:18:33.057.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLorenza Penengo
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-06 06:02:48ID requested
12023-10-09 03:13:52announced
22023-11-14 08:18:33announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: homo sapiens, orbitrap fusion lumos mass spectrometer, ISG15, ubiquitiin, DNA replication
Contact List
Lorenza Penengo
contact affiliationPenengo Lab, Institute of Molecular Cancer Research, University of Zurich, Switzerland
contact emailpenengo@imcr.uzh.ch
lab head
Lorenza Penengo
contact affiliationUniversity of Zurich
contact emailpenengo@imcr.uzh.ch
dataset submitter
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Dataset FTP location
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PRIDE project URI
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