PXD038656 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | DNA Replication Stress Due to Loss of R-Loops in Myelodysplastic Syndromes with SF3B1 Mutation |
Description | Myelodysplastic syndromes (MDS) with mutated SF3B1 gene have many features including a favorable outcome that are distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we show that SF3B1-mutated MDS are characterized by a dramatically reduced R-loop formation predominating in gene bodies, which tightly associates with reduced retention of introns specifically found in SF3B1-mutated, but not in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibited augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation, which were recapitulated in murine Sf3b1K700E/+ proerythroblasts. Importantly, R-loop formation was restored by histone deacetylase inhibition using SAHA/vorinostat, which improved Sf3b1K700E/+ erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress is a hallmark of SF3B1- mutated MDS ineffective erythropoiesis, which could be used as a new therapeutic target. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-29 |
AnnouncementXML | Submission_2024-05-29_02:24:07.385.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Marjorie Leduc |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-07 12:07:40 | ID requested | |
⏵ 1 | 2024-05-29 02:24:07 | announced | |
Publication List
Keyword List
submitter keyword: R-loops, SF3B1,myelodysplastic syndromes, replication |
Contact List
Michaela Fontenay |
contact affiliation | 1 Université Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin 2 Equipe labellisée par la Fondation pour la Recherche Médicale, Paris, France 3 Laboratoire d’excellence du Globule Rouge GR-Ex, Université Paris Cité, Paris, France 4 Assistance Publique-Hôpitaux de Paris.Centre-Université Paris Cité, Hôpital Cochin, Laboratory of Hematology, Paris, France |
contact email | michaela.fontenay@inserm.fr |
lab head | |
Marjorie Leduc |
contact affiliation | Plateforme protéomique 3P5, Université de Paris, Institut Cochin, INSERM, CNRS, |
contact email | marjorie.leduc@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038656
- Label: PRIDE project
- Name: DNA Replication Stress Due to Loss of R-Loops in Myelodysplastic Syndromes with SF3B1 Mutation