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TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells

Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin liga...

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Autores principales: Scaramuzza, Shaun, Jones, Rebecca M., Sadurni, Martina Muste, Reynolds-Winczura, Alicja, Poovathumkadavil, Divyasree, Farrell, Abigail, Natsume, Toyoaki, Rojas, Patricia, Cuesta, Cyntia Fernandez, Kanemaki, Masato T., Saponaro, Marco, Gambus, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442450/
https://www.ncbi.nlm.nih.gov/pubmed/37604812
http://dx.doi.org/10.1038/s41467-023-40695-y
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author Scaramuzza, Shaun
Jones, Rebecca M.
Sadurni, Martina Muste
Reynolds-Winczura, Alicja
Poovathumkadavil, Divyasree
Farrell, Abigail
Natsume, Toyoaki
Rojas, Patricia
Cuesta, Cyntia Fernandez
Kanemaki, Masato T.
Saponaro, Marco
Gambus, Agnieszka
author_facet Scaramuzza, Shaun
Jones, Rebecca M.
Sadurni, Martina Muste
Reynolds-Winczura, Alicja
Poovathumkadavil, Divyasree
Farrell, Abigail
Natsume, Toyoaki
Rojas, Patricia
Cuesta, Cyntia Fernandez
Kanemaki, Masato T.
Saponaro, Marco
Gambus, Agnieszka
author_sort Scaramuzza, Shaun
collection PubMed
description Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts.
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spelling pubmed-104424502023-08-23 TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells Scaramuzza, Shaun Jones, Rebecca M. Sadurni, Martina Muste Reynolds-Winczura, Alicja Poovathumkadavil, Divyasree Farrell, Abigail Natsume, Toyoaki Rojas, Patricia Cuesta, Cyntia Fernandez Kanemaki, Masato T. Saponaro, Marco Gambus, Agnieszka Nat Commun Article Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts. Nature Publishing Group UK 2023-08-21 /pmc/articles/PMC10442450/ /pubmed/37604812 http://dx.doi.org/10.1038/s41467-023-40695-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Scaramuzza, Shaun
Jones, Rebecca M.
Sadurni, Martina Muste
Reynolds-Winczura, Alicja
Poovathumkadavil, Divyasree
Farrell, Abigail
Natsume, Toyoaki
Rojas, Patricia
Cuesta, Cyntia Fernandez
Kanemaki, Masato T.
Saponaro, Marco
Gambus, Agnieszka
TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title_full TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title_fullStr TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title_full_unstemmed TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title_short TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
title_sort traip resolves dna replication-transcription conflicts during the s-phase of unperturbed cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442450/
https://www.ncbi.nlm.nih.gov/pubmed/37604812
http://dx.doi.org/10.1038/s41467-023-40695-y
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