Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Pavel Talacko

LAB HEAD: Pavel Janscak

PROVIDER: PXD034331 | Pride | 2022-11-02

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	2a_20181123235655.raw	Raw
	2b_20181124011447.raw	Raw
	2c_20181124023239.raw	Raw
	2d_20181124035032.raw	Raw
	3a.raw	Raw

Items per page:

1 - 5 of 22

Similar Datasets

UAP56/DDX39b is a major co-transcriptional RNA-DNA helicase that unwinds harmful R loops genome-wide

Project description:Non-scheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R loop accumulation. One mechanism relies on the conserved THO complex in association with co-transcriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R loop removal. We show that UAP56 depletion causes R loop accumulation, R loop-mediated genome instability and replication fork stalling. We demonstrate an RNA-DNA helicase activity in UAP56 and that its overexpression suppresses R loops and genome instability induced by depleting 5 different unrelated factors. UAP56/DDX39B localizes to active chromatin and prevents the accumulation of RNA-DNA hybrids over the entire genome. We propose that, in addition to its RNA processing role, UAP56/DDX39B is a key helicase required to eliminate harmful co-transcriptional RNA structures that otherwise would block transcription and replication.

2020-05-25 | GSE127979 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [EdUseq]

Project description:Safeguarding replication fork stability in transcriptionally active regions, which require high DNA replication accuracy, is crucial for precise DNA replication and prevention of mutations. However, how cells ensure the stability of replication forks in these regions remains a critical challenge. Here, we discovered the pervasive existence of replication forks-associated RNA-DNA hybrids (RF-RDs) within transcriptionally active regions, where they act as a protective barrier against DNA2-mediated nascent DNA degradation and prevent replication fork collapse upon replication stress. Subsequently, the RNA helicase DDX39A dismantles RF-RDs, facilitating proper DNA2-mediated DNA resection and replication fork restart. Excessive dissolution of RF-RDs causes replication fork collapse and genomic instability, while insufficient dissolution of RF-RDs under replication stress increases fork stability, resulting in chemoresistance that can be reversed by eliminating RF-RDs. In summary, we elucidated the prevalence of RF-RDs at replication forks within transcriptionally active regions, revealed their pivotal role in safeguarding replication fork stability, and proposed that targeting RF-RDs holds promise for augmenting chemotherapeutic efficacy.

2024-12-18 | GSE281980 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [WGRS]

2024-12-18 | GSE254535 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [REFORC]

2024-12-18 | GSE254306 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [RNA_seq]

2024-12-18 | GSE254199 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [EdU_seq]

2024-12-18 | GSE254196 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [gH2AX_ChIPseq]

2024-12-18 | GSE254195 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [HeLa REFORC]

2024-12-18 | GSE281981 | GEO

Replication Fork-Associated RNA-DNA Hybrids Safeguard Genomic Stability in Transcriptionally Active Regions [DNA2_MRE11_ChIPseq]

2024-12-18 | GSE254534 | GEO

RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart

Project description:R-loops represent a major source of replication stress but the mechanism by which these structures impede fork progression remains unclear. To address this question, we monitored fork progression, arrest and restart in S. cerevisiae cells lacking RNase H1 and H2, two enzymes responsible for degrading RNA:DNA hybrids. We found that while RNase H-deficient cells could replicate normally their chromosomes under unchallenged growth conditions, their replication was impaired when exposed to hydroxyurea (HU) or methyl methanesulfonate (MMS). Indeed, these cells exhibited increased levels of RNA:DNA hybrids at stalled forks and were unable to generate RPA-coated single-stranded (ssDNA), an important postreplicative step in resuming replication. Similar impairments in nascent DNA resection at HU-arrested forks were observed in human cells lacking RNase H2. However, the addition of triptolide, an inhibitor of transcription that induces RNA polymerase degradation, fully restored fork resection. Taken together, these data indicate that RNA:DNA hybrids not only act as barriers to replication forks, but also interfere with postreplicative fork repair mechanisms if not promptly degraded by RNase H.

2023-10-14 | GSE215896 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data