PXD031770-1

PXD031770 is an original dataset announced via ProteomeXchange.

Title	ISG15 Conjugation to Proteins on Nascent DNA Mitigates DNA Replication Stress
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2022-10-12
AnnouncementXML	Submission_2022-10-12_09:48:06.306.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ZhuoningLi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-21 02:42:11	ID requested
⏵ 1	2022-10-12 09:48:06	announced

Dataset with its publication pending

submitter keyword: Mre11, ISG15

JohnPetrini
contact affiliation	Molecular Biology Program, Memorial Sloan-Kettering Cancer Center
contact email	petrinij@mskcc.org
lab head
ZhuoningLi
contact affiliation	MSKCC
contact email	liz2@mskcc.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031770
     1. Label: PRIDE project
     2. Name: ISG15 Conjugation to Proteins on Nascent DNA Mitigates DNA Replication Stress