Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/10451/54188 |
Resumo: | © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
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Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Here, we show that ATR signaling is increased after depletion of the RNAPII phosphatase PNUTS-PP1, which dephosphorylates RNAPII in its carboxy-terminal domain (CTD). High ATR signaling was observed in the absence and presence of ionizing radiation, replication stress and even in G1, but did not correlate with DNA damage or RPA chromatin loading. R-loops were enhanced, but overexpression of EGFP-RNaseH1 only slightly reduced ATR signaling after PNUTS depletion. However, CDC73, which interacted with RNAPII in a phospho-CTD dependent manner, was required for the high ATR signaling, R-loop formation and for activation of the endogenous G2 checkpoint after depletion of PNUTS. In addition, ATR, RNAPII and CDC73 co-immunoprecipitated. Our results suggest a novel pathway involving RNAPII, CDC73 and PNUTS-PP1 in ATR signaling and give new insight into the diverse functions of ATR.Norwegian Cancer Society [3367910]; South-Eastern Norway Health Authorities [2014035, 2013017]; Norwegian Research Council [275918]; EEA Czech-Norwegian Research Programme (Norwegian Financial Mechanism 2009–2014 and the Ministry of Education, Youth and Sports [Project Contract no. MSMT-22477/2014 (7F14061)]. Funding for open access charge: Norwegian Research Council.Oxford University PressRepositório da Universidade de LisboaLandsverk, Helga B.Sandquist, Lise E.Sridhara, Sree Rama ChaitanyaRødland, Gro EliseSabino, João C.de Almeida, Sérgio F.Grallert, BeataTrinkle-Mulcahy, LauraSyljuåsen, Randi G.2022-08-25T10:43:43Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54188engNucleic Acids Res. 2019 Feb 28;47(4):1797-18130305-104810.1093/nar/gky12331362-4962info: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:RCAAP2023-11-08T16:59:47Zoai:repositorio.ul.pt:10451/54188Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:40.457355Repositório 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 |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| title |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| spellingShingle |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 Landsverk, Helga B. |
| title_short |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| title_full |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| title_fullStr |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| title_full_unstemmed |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| title_sort |
Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1 |
| author |
Landsverk, Helga B. |
| author_facet |
Landsverk, Helga B. Sandquist, Lise E. Sridhara, Sree Rama Chaitanya Rødland, Gro Elise Sabino, João C. de Almeida, Sérgio F. Grallert, Beata Trinkle-Mulcahy, Laura Syljuåsen, Randi G. |
| author_role |
author |
| author2 |
Sandquist, Lise E. Sridhara, Sree Rama Chaitanya Rødland, Gro Elise Sabino, João C. de Almeida, Sérgio F. Grallert, Beata Trinkle-Mulcahy, Laura Syljuåsen, Randi G. |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Landsverk, Helga B. Sandquist, Lise E. Sridhara, Sree Rama Chaitanya Rødland, Gro Elise Sabino, João C. de Almeida, Sérgio F. Grallert, Beata Trinkle-Mulcahy, Laura Syljuåsen, Randi G. |
| description |
© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2022-08-25T10:43:43Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/54188 |
| url |
http://hdl.handle.net/10451/54188 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Nucleic Acids Res. 2019 Feb 28;47(4):1797-1813 0305-1048 10.1093/nar/gky1233 1362-4962 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Oxford University Press |
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Oxford University Press |
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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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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