Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair.

Détails

ID Serval
serval:BIB_A6E0AC7C0049
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair.
Périodique
The EMBO journal
Auteur⸱e⸱s
Glousker G., Briod A.S., Quadroni M., Lingner J.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
01/12/2020
Peer-reviewed
Oui
Volume
39
Numéro
23
Pages
e104500
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through genetics and proteomics, discovering that a complete absence of POT1 leads to severe telomere maintenance defects that had not been anticipated from previous depletion studies in human cells. Conditional deletion of POT1 in HEK293E cells gives rise to rapid telomere elongation and length heterogeneity, branched telomeric DNA structures, telomeric R-loops, and telomere fragility. We determine the telomeric proteome upon POT1-loss, implementing an improved telomeric chromatin isolation protocol. We identify a large set of proteins involved in nucleic acid metabolism that engage with telomeres upon POT1-loss. Inactivation of the homology-directed repair machinery suppresses POT1-loss-mediated telomeric DNA defects. Our results unravel as major function of human POT1 the suppression of telomere instability induced by homology-directed repair.
Mots-clé
Cell Cycle/physiology, DNA/metabolism, DNA, Single-Stranded, Gene Knockout Techniques, HEK293 Cells, HeLa Cells, Humans, Phenotype, Proteome, Recombinational DNA Repair/genetics, Recombinational DNA Repair/physiology, Telomere/metabolism, Telomere-Binding Proteins/genetics, Telomere-Binding Proteins/metabolism, Transcriptome, DNA damage response, POT1, R-loops, homologous recombination, telomeric proteome
Pubmed
Web of science
Création de la notice
23/11/2020 16:44
Dernière modification de la notice
23/10/2021 5:38
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