PXD024517 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | R-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 |
Description | Transcription 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-04-11 |
AnnouncementXML | Submission_2023-04-11_06:30:52.674.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | PetraBeli |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-03-04 03:58:01 | ID requested | |
1 | 2021-11-25 08:58:53 | announced | |
⏵ 2 | 2023-04-11 06:30:53 | announced | 2023-04-11: Updated project metadata. |
Publication List
Mosler T, Conte F, Longo GMC, Mikicic I, Kreim N, M, ö, ckel MM, Petrosino G, Flach J, Barau J, Luke B, Roukos V, Beli P, R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability. Nat Commun, 12(1):7314(2021) [pubmed] |
Keyword List
submitter keyword: R-loop DDX41 |
Contact List
PetraBeli |
contact affiliation | Institute of Molecular Biology (IMB), Mainz, Germany |
contact email | p.beli@imb-mainz.de |
lab head | |
PetraBeli |
contact affiliation | Institute of Molecular Biology (IMB), Mainz, Germany |
contact email | p.beli@imb-mainz.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024517
- Label: PRIDE project
- Name: R-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