PXD070472 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The genetic and biochemical basis of human leading strand synthesis |
| Description | The maintenance of genome stability requires efficient leading strand synthesis by DNA Polymerase Epsilon (Pol). By performing CRISPR genetic screens in cells lacking the POLE4 subunit of Pol we define a genetic map of the factors required to support Pol function in the absence of its accessory subunits. A set of genes involved in iron metabolism emerge as required to sustain Iron Sulphur Cluster (ISC)-dependent Pol activity. We then dissect a synthetic lethal interaction between POLE3-POLE4 and the CHTF18-RFC2/5 complex. By combining cell biology, structural modelling and biochemistry, we define the existence of two tiers of regulation of Pol processivity: leading strand-specific loading of PCNA by CHTF18-RFC2/5 and “gripping” of newly synthesised dsDNA by POLE3-POLE4. The combined loss of these functions is incompatible with leading strand synthesis and viability. In summary, we describe the biochemical basis of human leading strand synthesis and the consequence of its dysfunction in genome stability. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-01-19 |
| AnnouncementXML | Submission_2026-01-18_16:26:29.683.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Sarah Maslen |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-11-07 13:41:33 | ID requested | |
| ⏵ 1 | 2026-01-18 16:26:30 | announced | |
Publication List
| 10.1038/s41467-025-67107-7; |
| Agnarelli A, Buckley-Benbow L, Ozgencil M, Lad M, Ampah KK, Kalinka A, Belan O, Maslen S, Skehel MJ, Walter D, Day M, Bellelli R, The genetic and biochemical basis of human leading strand synthesis. Nat Commun, 17(1):412(2025) [pubmed] |
Keyword List
| submitter keyword: The genetic and biochemical basis of human leading strand synthesis |
Contact List
| Dr. Roberto Bellelli |
|---|
| contact affiliation | Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M 6BQ, London, UK |
| contact email | r.bellelli@qmul.ac.uk |
| lab head | |
| Sarah Maslen |
|---|
| contact affiliation | The Francis Crick Institute |
| contact email | sarah.maslen@crick.ac.uk |
| dataset submitter | |
Full Dataset Link List
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://ftp.pride.ebi.ac.uk/pride/data/archive/2026/01/PXD070472 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD070472
- Label: PRIDE project
- Name: The genetic and biochemical basis of human leading strand synthesis
