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Authors: Pérez-Martínez, Lara
Öztürk, Merve
Butter, Falk
Luke, Brian
Title: Npl3 stabilizes R-loops at telomeres to prevent accelerated replicative senescence
Online publication date: 6-Aug-2021
Language: english
Abstract: Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R-loops become stabilized at critically short telomeres to promote their elongation through homology-directed repair (HDR), thereby counteracting senescence onset. Using a non-bias proteomic approach to detect telomere binding factors, we identified Npl3, an RNA-binding protein previously implicated in multiple RNA biogenesis processes. Using chromatin immunoprecipitation and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates with telomeres in an R-loop-dependent manner, as changes in R-loop levels, for example, at short telomeres, modulate the recruitment of Npl3 to chromosome ends. Through a series of genetic and biochemical approaches, we reveal that Npl3 binds to TERRA and stabilizes R-loops at short telomeres, which in turn promotes HDR and prevents premature replicative senescence onset. This may have implications for diseases associated with excessive telomere shortening.
DDC: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 10 Biologie
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: EMBO reports
Pages or article number: e49087
Publisher: Wiley
Publisher place: Hoboken, NJ u.a.
Issue date: 2020
ISSN: 1469-3178
Publisher URL:
Publisher DOI: 10.15252/embr.201949087
Appears in collections:JGU-Publikationen

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