PXD045154-1

PXD045154 is an original dataset announced via ProteomeXchange.

Title	Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15
Description	DNA 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.
HostingRepository	PRIDE
AnnounceDate	2023-10-09
AnnouncementXML	Submission_2023-10-09_03:13:52.119.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LorenzaPenengo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-06 06:02:48	ID requested
⏵ 1	2023-10-09 03:13:52	announced
2	2023-11-14 08:18:33	announced	2023-11-14: Updated project metadata.

submitter keyword: homo sapiens, orbitrap fusion lumos mass spectrometer, ISG15, ubiquitiin, DNA replication

LorenzaPenengo
contact affiliation	Penengo Lab, Institute of Molecular Cancer Research, University of Zurich, Switzerland
contact email	penengo@imcr.uzh.ch
lab head
LorenzaPenengo
contact affiliation	University of Zurich
contact email	penengo@imcr.uzh.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045154
     1. Label: PRIDE project
     2. Name: Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15