<<< Full experiment listing

PXD024517

PXD024517 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleR-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instabilityR-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
DescriptionTranscription can pose a threat to genomic stability through the formation of R-loops that obstruct the progression of replication forks. R-loops are three-stranded nucleic acid structures formed by an RNA-DNA hybrid with a displaced non-template DNA strand. We developed RDProx to identify proteins that regulate R-loops in human cells. RDProx relies on the expression of the hybrid-binding domain (HBD) of Ribonuclease H1 (RNaseH1) fused to the ascorbate peroxidase (APEX2), which permits mapping of the R-loop proximal proteome using quantitative mass spectrometry. We associated R-loop regulation with different cellular proteins and identified a role of the tumor suppressor DEAD box protein 41 (DDX41) in opposing R-loop-dependent genomic instability. Depletion of DDX41 resulted in replication stress, double strand breaks and increased inflammatory signaling. Furthermore, DDX41 opposes accumulation of R-loops at gene promoters and its loss leads to upregulated expression of TGFβ and NOTCH signaling genes. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia (AML) in adulthood. We propose that accumulation of co-transcriptional R-loops, associated gene expression changes and inflammatory response contribute to the development of familial AML with mutated DDX41.
HostingRepositoryPRIDE
AnnounceDate2021-11-25
AnnouncementXMLSubmission_2021-11-25_08:58:53.507.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPetra Beli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-04 03:58:01ID requested
12021-11-25 08:58:53announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: R-loop DDX41
Contact List
Petra Beli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
lab head
Petra Beli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
[ + ]