PXD034331

PXD034331 is an original dataset announced via ProteomeXchange.

Title	DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells
Description	R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co- transcriptionally in the opposite orientation to replication fork progression. Recent studies have shown that replication forks stalled by co-transcription R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds RNA:DNA hybrids in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81-LIG4 pathway for resolution of R-loop-mediated transcription- replication conflicts, which may be involved in R-loop unwinding.
HostingRepository	PRIDE
AnnounceDate	2022-11-02
AnnouncementXML	Submission_2022-11-02_06:06:04.664.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034331
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	PavelTalacko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-06 01:09:29	ID requested
⏵ 1	2022-11-02 06:06:05	announced

10.6019/PXD034331;

submitter keyword: DNA replication stress

R-loop

Helicase

Genomic instability

Transcription

PavelJanscak
contact affiliation	Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
contact email	pjanscak@imcr.uzh.ch
lab head
PavelTalacko
contact affiliation	BIOCEV, Faculty of Science, Charles University in Prague
contact email	pavel.talacko@natur.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034331
     1. Label: PRIDE project
     2. Name: DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells