PXD002626

PXD002626 is an original dataset announced via ProteomeXchange.

Title	Peroxiredoxin 1 protects telomeres from oxidative damage preserving chromosome ends for extension by telomerase
Description	With the increase of atmospheric oxygen 2.3 billion years ago, mechanisms evolved to mitigate the toxic effects of oxygen radicals. Telomeres appear particularly susceptible to oxidative damage, which leads to cellular and organismal aging, cancer, cardiac failure and other diseases. Specific mechanisms of telomere protection from oxidative damage and the molecular consequences of the damage have not been described. Here, we identify the antioxidant enzyme peroxiredoxin 1 (PRDX1) enriched in telomeric chromatin in S and G2 phases of the cell cycle during which telomeres become replicated. PRDX1 depletion leads to oxidative damage of telomeric DNA without affecting the bulk of genomic DNA. The oxidized nucleotide 8-oxo-2’deoxyguanosine-5’-triphosphate (8oxodGTP) can be incorporated by telomerase into telomeric repeats but it mediates premature chain termination when incorporated as first G in the telomeric 5’-TTAGGG-3’ sequence. In dependency of the alignment position within the telomerase RNA template, terminus 8oxoG containing DNA substrates also completely block extension by telomerase. We propose two major mechanisms by which PRDX1 counteracts telomere damage and aging. In safeguarding telomeres from oxygen radicals, PRDX1 prevents DNA damage, telomere replication defects and mutations that will perturb recognition of telomeric DNA by shelterin components. In preventing modification of the telomeric DNA substrate and the dNTP pool, PRDX1 preserves telomeres for elongation by telomerase.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:00.198.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Romain Hamelin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-29 05:42:29	ID requested
1	2016-12-07 05:48:25	announced
2	2017-01-02 09:24:41	announced	Updated publication reference for PubMed record(s): 28009281.
3	2017-10-24 02:04:42	announced	Updated project metadata.
⏵ 4	2024-10-22 04:05:02	announced	2024-10-22: Updated project metadata.

Aeby E, Ahmed W, Redon S, Simanis V, Lingner J, Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase. Cell Rep, 17(12):3107-3114(2016) [pubmed]

10.1016/j.celrep.2016.11.071;

curator keyword: Biological, Biomedical

submitter keyword: Peroxiredoxin 1

telomeres

oxidative damage

telomerase

Marc Moniatte
contact affiliation	EPFL SV SSV-GE AI 0149 (Bâtiment AI) Station 19 CH-1015 Lausanne
contact email	marc.moniatte@epfl.ch
lab head
Romain Hamelin
contact affiliation	PCF
contact email	romain.hamelin@epfl.ch
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/2016/12/PXD002626

PRIDE project URI

• PRIDE
  1. PXD002626
     1. Label: PRIDE project
     2. Name: Peroxiredoxin 1 protects telomeres from oxidative damage preserving chromosome ends for extension by telomerase