PXD035689

PXD035689 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:18:30.149.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD035689
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Gregory Tombline
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

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.

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]

submitter keyword: LMNA, centenarian, longevity,SIRT6, ADP-ribosylation, aging

Vera Gorbunova
contact affiliation	Department of Biology University of Rochester Rochester, NY , USA
contact email	vera.gorbunova@rochester.edu
lab head
Gregory Tombline
contact affiliation	University of Rochester
contact email	gregtombline@gmail.com
dataset submitter

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

• PRIDE
  1. PXD035689
     1. Label: PRIDE project
     2. Name: A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A