The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/54541 |
Resumo: | 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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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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:58Zoai:repositorio.ul.pt:10451/54541Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:20.975023Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134605240958976 |