PXD035689-1
PXD035689 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A |
Description | Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in the regulation of aging and metabolism. Targeted sequencing identified a SIRT6 allele containing two linked substitutions (N308K/A313S) as enriched in Ashkenazi Jewish (AJ) centenarians as compared to AJ control individuals. Characterization of this SIRT6 (centSIRT6) allele demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double strand break repair, and more robust cancer cell killing compared to the wild type. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-21 |
AnnouncementXML | Submission_2022-10-21_08:05:27.137.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD035689 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | GregoryTombline |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-08-01 09:29:15 | ID requested | |
⏵ 1 | 2022-10-21 08:05:27 | announced | |
2 | 2023-11-14 07:18:31 | announced | 2023-11-14: Updated project metadata. |
Publication List
10.6019/PXD035689; |
Simon M, Yang J, Gigas J, Earley EJ, Hillpot E, Zhang L, Zagorulya M, Tombline G, Gilbert M, Yuen SL, Pope A, Van Meter M, Emmrich S, Firsanov D, Athreya A, Biashad SA, Han J, Ryu S, Tare A, Zhu Y, Hudgins A, Atzmon G, Barzilai N, Wolfe A, Moody K, Garcia BA, Thomas DD, Robbins PD, Vijg J, Seluanov A, Suh Y, Gorbunova V, A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. EMBO J, 41(21):e110393(2022) [pubmed] |
Keyword List
submitter keyword: LMNA, centenarian, longevity,SIRT6, ADP-ribosylation, aging |
Contact List
VeraGorbunova | |
---|---|
contact affiliation | Department of Biology University of Rochester Rochester, NY , USA |
contact email | vera.gorbunova@rochester.edu |
lab head | |
GregoryTombline | |
contact affiliation | University of Rochester |
contact email | gregtombline@gmail.com |
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/2022/10/PXD035689 |
PRIDE project URI |
Repository Record List
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