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  The chromatin remodelling factor ATRX suppresses R-loops in transcribed telomeric repeats

Nguyen, D. T., Voon, H. P. J., Xella, B., Scott, C., Clynes, D., Babbs, C., et al. (2017). The chromatin remodelling factor ATRX suppresses R-loops in transcribed telomeric repeats. EMBO Reports, 18, 914-928. doi:10.15252/embr.201643078.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BFD9-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C2A0-A
Genre: Journal Article

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 Creators:
Nguyen, Diu TT1, Author
Voon, Hsiao Phin J1, Author
Xella, Barbara1, Author
Scott, Caroline1, Author
Clynes, David1, Author
Babbs, Christian1, Author
Ayyub, Helena1, Author
Kerry, Jon1, Author
Sharpe, Jacqueline A1, Author
Sloane‐Stanley, Jackie A1, Author
Butler, Sue1, Author
Fisher, Chris A1, Author
Gray, Nicki E1, Author
Jenuwein, Thomas2, Author              
Higgs, Douglas R1, Author
Gibbons, Richard J1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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Free keywords: ATRX, G-quadruplex, R-loops, telomeres
 Abstract: ATRX is a chromatin remodelling factor found at a wide range of tandemly repeated sequences including telomeres (TTAGGG)n. ATRX mutations are found in nearly all tumours that maintain their telomeres via the alternative lengthening of telomere (ALT) pathway, and ATRX is known to suppress this pathway. Here, we show that recruitment of ATRX to telomeric repeats depends on repeat number, orientation and, critically, on repeat transcription. Importantly, the transcribed telomeric repeats form RNA–DNA hybrids (R‐loops) whose abundance correlates with the recruitment of ATRX. Here, we show loss of ATRX is also associated with increased R‐loop formation. Our data suggest that the presence of ATRX at telomeres may have a central role in suppressing deleterious DNA secondary structures that form at transcribed telomeric repeats, and this may account for the increased DNA damage, stalling of replication and homology‐directed repair previously observed upon loss of ATRX function.

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Language(s): eng - English
 Dates: 2017-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.15252/embr.201643078
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Title: EMBO Reports
  Other : EMBO Rep.
Source Genre: Journal
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Publ. Info: Oxford, UK : Published for EMBO by Oxford University Press
Pages: - Volume / Issue: 18 Sequence Number: - Start / End Page: 914 - 928 Identifier: ISSN: 1469-221X
CoNE: https://pure.mpg.de/cone/journals/resource/110978984569661