DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs

Rossiello, Francesca, Aguado, Julio, Sepe, Sara, Iannelli, Fabio, Nguyen, Quan, Pitchiaya, Sethuramasundaram, Carninci, Piero and Di Fagagna, Fabrizio d’Adda (2017) DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs. Nature Communications, 8 . doi:10.1038/ncomms13980


Author Rossiello, Francesca
Aguado, Julio
Sepe, Sara
Iannelli, Fabio
Nguyen, Quan
Pitchiaya, Sethuramasundaram
Carninci, Piero
Di Fagagna, Fabrizio d’Adda
Title DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-02-27
Sub-type Article (original research)
DOI 10.1038/ncomms13980
Open Access Status DOI
Volume 8
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2018
Language eng
Formatted abstract
The DNA damage response (DDR) is a set of cellular events that follows the generation of DNA damage. Recently, site-specific small non-coding RNAs, also termed DNA damage response RNAs (DDRNAs), have been shown to play a role in DDR signalling and DNA repair. Dysfunctional telomeres activate DDR in ageing, cancer and an increasing number of identified pathological conditions. Here we show that, in mammals, telomere dysfunction induces the transcription of telomeric DDRNAs (tDDRNAs) and their longer precursors from both DNA strands. DDR activation and maintenance at telomeres depend on the biogenesis and functions of tDDRNAs. Their functional inhibition by sequence-specific antisense oligonucleotides allows the unprecedented telomere-specific DDR inactivation in cultured cells and in vivo in mouse tissues. In summary, these results demonstrate that tDDRNAs are induced at dysfunctional telomeres and are necessary for DDR activation and they validate the viability of locus-specific DDR inhibition by targeting DDRNAs.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 21 Mar 2017, 00:25:23 EST by Web Cron on behalf of Learning and Research Services (UQ Library)