PXD045110
PXD045110 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 arising from defective DNA damage response or mitotic chromosomal imbalance can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and genomic instability-associated diseases, the catalogue of genetic players that regulate their generation remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n=71) or decreases (n=74) MN formation, including many whose orthologs are linked to human disease. We found that Dscc1 (DNA replication and sister chromatid cohesion 1) null mice, which had the highest number of MN, also displayed a range of phenotypes characteristic of cohesinopathy patients. After validating the DSCC1-MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue 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 reveals a wealth of novel factors involved in maintaining genomic stability and shows how this information can be used to uncover mechanisms relevant to human disease biology. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:14:52.300.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Graeme Benstead-Hume |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-09-05 08:04:40 | ID requested | |
1 | 2023-11-17 04:51:46 | announced | |
2 | 2024-03-18 07:28:03 | announced | 2024-03-18: Updated project metadata. |
⏵ 3 | 2024-10-22 06:14:53 | 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: genomic stability,micronucleus formation |
Contact List
Jyoti Choudhary | |
---|---|
contact affiliation | Functional Proteomic, ICR |
contact email | jyoti.choudhary@icr.ac.uk |
lab head | |
Graeme Benstead-Hume | |
contact affiliation | ICR |
contact email | ghume@icr.ac.uk |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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