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PXD031770

PXD031770 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleISG15 Conjugation to Proteins on Nascent DNA Mitigates DNA Replication Stress
DescriptionThe pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among double strand break (DSB) repair proteins for its association with the DNA replication fork. Here we show that Mre11 complex inactivation causes DNA replication stress and changes in the abundance of proteins associated with nascent DNA. One of the most highly enriched proteins at the DNA replication fork upon Mre11 complex inactivation was the ubiquitin like protein ISG15. Mre11 complex deficiency and drug induced replication stress both led to the accumulation of cytoplasmic DNA and the subsequent activation of innate immune signaling via cGAS-STING-Tbk1. This led to ISG15 induction and protein ISGylation, including constituents of the replication fork. ISG15 plays a direct role in preventing replication stress. Deletion of ISG15 was associated with replication fork stalling, tonic ATR activation, genomic aberrations, and sensitivity to aphidicolin. These data reveal a previously unrecognized role for ISG15 in mitigating DNA replication stress and promoting DNA replication fidelity.
HostingRepositoryPRIDE
AnnounceDate2022-10-12
AnnouncementXMLSubmission_2022-10-12_09:48:06.306.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZhuoningLi
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-21 02:42:11ID requested
12022-10-12 09:48:06announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Mre11, ISG15
Contact List
JohnPetrini
contact affiliationMolecular Biology Program, Memorial Sloan-Kettering Cancer Center
contact emailpetrinij@mskcc.org
lab head
ZhuoningLi
contact affiliationMSKCC
contact emailliz2@mskcc.org
dataset submitter
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Dataset FTP location
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