PXD026917-1
PXD026917 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Fused in sarcoma regulates DNA replication timing and progression |
| Description | Fused-in-sarcoma (FUS) encodes an RNA-binding protein with diverse roles in transcriptional activation and RNA splicing. While oncogenic fusions of FUS and transcription factor DNA-binding domains are associated with soft tissue sarcomas, dominant mutations in FUS cause amyotrophic lateral sclerosis (ALS). FUS has also been implicated in genome maintenance. However, the underlying mechanisms are unknown. Here, we applied gene editing, functional reconstitution and integrated proteomic and transcriptomics to illuminate roles for FUS in DNA replication and repair. Consistent with a supportive role in DNA double-strand break (DSB) repair FUS deficient cells exhibited subtle alterations in the recruitment and retention of DSB-associated factors, including 53BP1 and BRCA1. FUS-/- cells also exhibited reduced proliferative potential that correlated with reduced replication fork speed, diminished loading of pre-replication complexes, enhanced micronucleus formation, and attenuated expression and splicing of S-phase associated genes. Finally, FUS-deficient cells exhibited genome-wide alterations in DNA replication timing that were reversed upon reeexpression of FUS cDNA. FUS-dependent replication domains were enriched in transcriptionally active chromatin and FUS was required for the timely replication of transcriptionally active DNA. These findings suggest that alterations DNA replication kinetics and programming contribute to genome instability and functional defects in FUS deficient cells. |
| HostingRepository | MassIVE |
| AnnounceDate | 2021-06-24 |
| AnnouncementXML | Submission_2021-06-24_12:59:42.806.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | WEIYAN JIA |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | LTQ Orbitrap |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-06-24 11:41:02 | ID requested | |
| ⏵ 1 | 2021-06-24 12:59:43 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: FUS, Replication Timing, chromatin binding proteins |
Contact List
| Randal Tibbetts | |
|---|---|
| contact affiliation | University of Wisconsin-Madison |
| contact email | rstibbetts@wisc.edu |
| lab head | |
| WEIYAN JIA | |
| contact affiliation | University of Wisconsin Madison |
| contact email | weiyanjia2008@gmail.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000087698/ |
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