R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Thorsten Mosler
- Francesca Conte
- Gabriel MC Longo
- Ivan Mikicic
- Nastasja Kreim
- Martin M Moeckel
- Giuseppe Petrosino
- Johanna Flach
- Joan Barau
- Brian Luke
- Vassilis Roukos
- Petra Beli
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000731101200022&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/s41467-021-27530-y
- eISSN
- 2041-1723
- Externe Identifier
- Clarivate Analytics Document Solution ID: XP8HQ
- PubMed Identifier: 34916496
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- NATURE COMMUNICATIONS
- Artikelnummer
- ARTN 7314
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
- Sub types
- Article
- Ausgabe der Zeitschrift
- 12
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct 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 RNA–DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DDX41 in opposing R-loop and double strand DNA break accumulation in promoters. DDX41 is enriched in promoter regions in vivo, and can unwind RNA–DNA hybrids in vitro. R-loop accumulation upon loss of DDX41 is accompanied with replication stress, an increase in the formation of double strand DNA breaks and transcriptome changes associated with the inflammatory response. Germline loss-of-function mutations in <jats:italic>DDX41</jats:italic> lead to predisposition to acute myeloid leukemia in adulthood. We propose that R-loop accumulation and genomic instability-associated inflammatory response may contribute to the development of familial AML with mutated DDX41.</jats:p>
- Autoren
- Thorsten Mosler
- Francesca Conte
- Gabriel MC Longo
- Ivan Mikicic
- Nastasja Kreim
- Martin M Möckel
- Giuseppe Petrosino
- Johanna Flach
- Joan Barau
- Brian Luke
- Vassilis Roukos
- Petra Beli
- DOI
- 10.1038/s41467-021-27530-y
- eISSN
- 2041-1723
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nature Communications
- Sprache
- en
- Artikelnummer
- 7314
- Online publication date
- 2021
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41467-021-27530-y
- Datum der Datenerfassung
- 2023
- Titel
- R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
- Ausgabe der Zeitschrift
- 12
Datenquelle: Crossref
- Abstract
- Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct 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 RNA-DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DDX41 in opposing R-loop and double strand DNA break accumulation in promoters. DDX41 is enriched in promoter regions in vivo, and can unwind RNA-DNA hybrids in vitro. R-loop accumulation upon loss of DDX41 is accompanied with replication stress, an increase in the formation of double strand DNA breaks and transcriptome changes associated with the inflammatory response. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia in adulthood. We propose that R-loop accumulation and genomic instability-associated inflammatory response may contribute to the development of familial AML with mutated DDX41.
- Addresses
- Institute of Molecular Biology (IMB), Mainz, Germany.
- Autoren
- Thorsten Mosler
- Francesca Conte
- Gabriel MC Longo
- Ivan Mikicic
- Nastasja Kreim
- Martin M Möckel
- Giuseppe Petrosino
- Johanna Flach
- Joan Barau
- Brian Luke
- Vassilis Roukos
- Petra Beli
- DOI
- 10.1038/s41467-021-27530-y
- eISSN
- 2041-1723
- Externe Identifier
- PubMed Identifier: 34916496
- PubMed Central ID: PMC8677849
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: 393547839-SFB 1361
- Deutsche Forschungsgemeinschaft: BE 5342/2-1-FOR 2800
- Open access
- true
- ISSN
- 2041-1723
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nature communications
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Genomic Instability
- DNA
- RNA
- Nucleic Acid Hybridization
- Proteomics
- Transcription, Genetic
- Nucleic Acid Conformation
- Genes, Tumor Suppressor
- Adult
- DEAD-box RNA Helicases
- DNA Breaks, Double-Stranded
- Leukemia, Myeloid, Acute
- Promoter Regions, Genetic
- Gene Knockdown Techniques
- HEK293 Cells
- R-Loop Structures
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2021
- Open access status
- Open Access
- Paginierung
- 7314
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2021
- Titel
- R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 12
Files
https://www.nature.com/articles/s41467-021-27530-y.pdf https://europepmc.org/articles/PMC8677849?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct 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 RNA-DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DDX41 in opposing R-loop and double strand DNA break accumulation in promoters. DDX41 is enriched in promoter regions in vivo, and can unwind RNA-DNA hybrids in vitro. R-loop accumulation upon loss of DDX41 is accompanied with replication stress, an increase in the formation of double strand DNA breaks and transcriptome changes associated with the inflammatory response. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia in adulthood. We propose that R-loop accumulation and genomic instability-associated inflammatory response may contribute to the development of familial AML with mutated DDX41.
- Date of acceptance
- 2021
- Autoren
- Thorsten Mosler
- Francesca Conte
- Gabriel MC Longo
- Ivan Mikicic
- Nastasja Kreim
- Martin M Möckel
- Giuseppe Petrosino
- Johanna Flach
- Joan Barau
- Brian Luke
- Vassilis Roukos
- Petra Beli
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/34916496
- DOI
- 10.1038/s41467-021-27530-y
- eISSN
- 2041-1723
- Externe Identifier
- PubMed Central ID: PMC8677849
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nat Commun
- Schlüsselwörter
- Adult
- Cell Line, Tumor
- DEAD-box RNA Helicases
- DNA
- DNA Breaks, Double-Stranded
- Gene Knockdown Techniques
- Genes, Tumor Suppressor
- Genomic Instability
- HEK293 Cells
- Humans
- Leukemia, Myeloid, Acute
- Nucleic Acid Conformation
- Nucleic Acid Hybridization
- Promoter Regions, Genetic
- Proteomics
- R-Loop Structures
- RNA
- Transcription, Genetic
- Sprache
- eng
- Country
- England
- Paginierung
- 7314
- PII
- 10.1038/s41467-021-27530-y
- Datum der Veröffentlichung
- 2021
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 12
Datenquelle: PubMed
- Abstract
- Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct 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 RNA-DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DDX41 in opposing R-loop and double strand DNA break accumulation in promoters. DDX41 is enriched in promoter regions in vivo, and can unwind RNA-DNA hybrids in vitro. R-loop accumulation upon loss of DDX41 is accompanied with replication stress, an increase in the formation of double strand DNA breaks and transcriptome changes associated with the inflammatory response. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia in adulthood. We propose that R-loop accumulation and genomic instability-associated inflammatory response may contribute to the development of familial AML with mutated DDX41.
- Autoren
- Thorsten Mosler
- Francesca Conte
- Gabriel MC Longo
- Ivan Mikicic
- Nastasja Kreim
- Martin M Möckel
- Giuseppe Petrosino
- Johanna Flach
- Joan Barau
- Brian Luke
- Vassilis Roukos
- Petra Beli
- DOI
- 10.1038/s41467-021-27530-y
- Zeitschrift
- Nature communications
- Artikelnummer
- 1
- Paginierung
- 7314 - 7314
- Datum der Veröffentlichung
- 2021
- Datum der Datenerfassung
- 2023
- Titel
- R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
- Sub types
- article
- Ausgabe der Zeitschrift
- 12
Datenquelle: Manual
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