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The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted

Bibliographic Details
Main Author: Silva, Bruno
Publication Date: 2022
Other Authors: Arora, Rajika, Azzalin, Claus Maria
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/54541
Summary: Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
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spelling The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restrictedMus81TERRAAlternative lengthening of telomeresTelomere transcriptionCopyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).A substantial number of human cancers are telomerase-negative and elongate physiologically damaged telomeres through a break-induced replication (BIR)-based mechanism known as alternative lengthening of telomeres (ALT). We recently demonstrated that inhibiting the transcription of the telomeric long noncoding RNA TERRA suppresses telomere damage and ALT features, indicating that telomere transcription is a main trigger of ALT activity. Here we show that experimentally increased TERRA transcription not only increases ALT features, as expected, but also causes rapid loss of telomeric DNA through a pathway that requires the endonuclease Mus81. Our data indicate that the ALT mechanism can endanger telomere integrity if not properly controlled and point to TERRA transcription as a uniquely versatile target for therapy.This work was supported by the Fundação para a Ciência e a Tecnologia (grants PTDC/BIA-MOL/6624/2020, PTDC/MED-ONC/7864/2020 to C.M.A. and B.S., and award 2021.00143.CEECIND to C.M.A.), European Molecular Biology Organization (grant IG3576 to C.M.A.), and LaCaixa Foundation (grant LCF/PR/HP21/52310016 to C.M.A.).National Academy of ScienceRepositório da Universidade de LisboaSilva, BrunoArora, RajikaAzzalin, Claus Maria2022-09-21T14:41:26Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54541engProc Natl Acad Sci USA. 2022 Sep 27;119(39):e22086691190027-842410.1073/pnas.22086691191091-6490info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:49:43Zoai:repositorio.ulisboa.pt:10451/54541Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:25:43.925142Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
title The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
spellingShingle The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
Silva, Bruno
Mus81
TERRA
Alternative lengthening of telomeres
Telomere transcription
title_short The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
title_full The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
title_fullStr The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
title_full_unstemmed The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
title_sort The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
author Silva, Bruno
author_facet Silva, Bruno
Arora, Rajika
Azzalin, Claus Maria
author_role author
author2 Arora, Rajika
Azzalin, Claus Maria
author2_role author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Silva, Bruno
Arora, Rajika
Azzalin, Claus Maria
dc.subject.por.fl_str_mv Mus81
TERRA
Alternative lengthening of telomeres
Telomere transcription
topic Mus81
TERRA
Alternative lengthening of telomeres
Telomere transcription
description Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
publishDate 2022
dc.date.none.fl_str_mv 2022-09-21T14:41:26Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54541
url http://hdl.handle.net/10451/54541
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Proc Natl Acad Sci USA. 2022 Sep 27;119(39):e2208669119
0027-8424
10.1073/pnas.2208669119
1091-6490
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Academy of Science
publisher.none.fl_str_mv National Academy of Science
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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