PXD030499
PXD030499 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Genetic determinants of genomic stability identified by comprehensive in vivo analyses of micronucleus formation |
Description | Genomic instability due to defective DNA damage response or arising from mitotic chromosomal imbalance can lead to sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of genomic instability associated diseases and ageing, the catalogue of genetic players that regulate their generation remains to be determined. Here analysed 996 mouse mutant lines, revealing 143 factors whose loss significantly increases (71) or decreases (72) MN formation. Most such genes, including the Dscc1 (DNA replication and sister chromatid cohesion 1) gene, have never been studied in mouse models. We found that Dscc1 defective mice were sub-viable and displayed phenotypes like the clinical characteristics of cohesinopathy patients. After validating the DSCC1-MN phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define its synthetic lethal and synthetic viable interactors. Perhaps surprisingly, we found that loss of Sirtuin 1 (SIRT1) can rebalance/rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of SMC3 (structural maintenance of chromosomes protein 3) protein acetylation. Our study provides a resource of novel factors involved in maintenance of genomic stability and shows how this information can be used to uncover mechanisms relevant to better understand disease biology. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:14:46.509.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | James Wright |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2021-12-17 13:31:04 | ID requested | |
1 | 2023-11-17 03:07:56 | announced | |
2 | 2024-03-18 07:27:54 | announced | 2024-03-18: Updated project metadata. |
⏵ 3 | 2024-10-22 06:14:47 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41586-023-07009-0; |
Adams DJ, Barlas B, McIntyre RE, Salguero I, van der Weyden L, Barros A, Vicente JR, Karimpour N, Haider A, Ranzani M, Turner G, Thompson NA, Harle V, Olvera-Le, รณ, n R, Robles-Espinoza CD, Speak AO, Geisler N, Weninger WJ, Geyer SH, Hewinson J, Karp NA, Fu B, Yang F, Kozik Z, Choudhary J, Yu L, van Ruiten MS, Rowland BD, Lelliott CJ, Del Castillo Velasco-Herrera M, Verstraten R, Bruckner L, Henssen AG, Rooimans MA, de Lange J, Mohun TJ, Arends MJ, Kentistou KA, Coelho PA, Zhao Y, Zecchini H, Perry JRB, Jackson SP, Balmus G, Tudor CL, Green AL, Mazzeo CI, Siragher E, Lillistone C, Gleeson D, Sethi D, Bayzetinova T, Burvill J, Habib B, Weavers L, Maswood R, Miklejewska E, Woods M, Grau E, Newman S, Sinclair C, Brown E, Doe B, Galli A, Ramirez-Solis R, Ryder E, Steel K, Bradley A, Skarnes WC, Adams DJ, Lafont D, Vancollie VE, McLaren RSB, Hughes-Hallett L, Rowley C, Sanderson E, Tuck E, Dabrowska M, Griffiths M, Gannon D, Cockle N, Kirton A, Bottomley J, Ingle C, Lelliott C, White JK, Genetic determinants of micronucleus formation in vivo. Nature, 627(8002):130-136(2024) [pubmed] |
Keyword List
submitter keyword: MS3, Human,TMT |
Contact List
Prof. Jyoti Choudhary | |
---|---|
contact affiliation | The Institute of Cancer Research |
contact email | jyoti.choudhary@icr.ac.uk |
lab head | |
James Wright | |
contact affiliation | The Institute of Cancer Research |
contact email | james.wright@icr.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/2023/11/PXD030499 |
PRIDE project URI |
Repository Record List
[ + ]