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E2F-dependent transcription determines replication capacity and S phase length

DNA replication timing is tightly regulated during S-phase. S-phase length is determined by DNA synthesis rate, which depends on the number of active replication forks and their velocity. Here, we show that E2F-dependent transcription, through E2F6, determines the replication capacity of a cell, def...

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Autores principales: Pennycook, Betheney R., Vesela, Eva, Peripolli, Silvia, Singh, Tanya, Barr, Alexis R., Bertoli, Cosetta, de Bruin, Robertus A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360579/
https://www.ncbi.nlm.nih.gov/pubmed/32665547
http://dx.doi.org/10.1038/s41467-020-17146-z
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author Pennycook, Betheney R.
Vesela, Eva
Peripolli, Silvia
Singh, Tanya
Barr, Alexis R.
Bertoli, Cosetta
de Bruin, Robertus A. M.
author_facet Pennycook, Betheney R.
Vesela, Eva
Peripolli, Silvia
Singh, Tanya
Barr, Alexis R.
Bertoli, Cosetta
de Bruin, Robertus A. M.
author_sort Pennycook, Betheney R.
collection PubMed
description DNA replication timing is tightly regulated during S-phase. S-phase length is determined by DNA synthesis rate, which depends on the number of active replication forks and their velocity. Here, we show that E2F-dependent transcription, through E2F6, determines the replication capacity of a cell, defined as the maximal amount of DNA a cell can synthesise per unit time during S-phase. Increasing or decreasing E2F-dependent transcription during S-phase increases or decreases replication capacity, and thereby replication rates, thus shortening or lengthening S-phase, respectively. The changes in replication rate occur mainly through changes in fork speed without affecting the number of active forks. An increase in fork speed does not induce replication stress directly, but increases DNA damage over time causing cell cycle arrest. Thus, E2F-dependent transcription determines the DNA replication capacity of a cell, which affects the replication rate, controlling the time it takes to duplicate the genome and complete S-phase.
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spelling pubmed-73605792020-07-20 E2F-dependent transcription determines replication capacity and S phase length Pennycook, Betheney R. Vesela, Eva Peripolli, Silvia Singh, Tanya Barr, Alexis R. Bertoli, Cosetta de Bruin, Robertus A. M. Nat Commun Article DNA replication timing is tightly regulated during S-phase. S-phase length is determined by DNA synthesis rate, which depends on the number of active replication forks and their velocity. Here, we show that E2F-dependent transcription, through E2F6, determines the replication capacity of a cell, defined as the maximal amount of DNA a cell can synthesise per unit time during S-phase. Increasing or decreasing E2F-dependent transcription during S-phase increases or decreases replication capacity, and thereby replication rates, thus shortening or lengthening S-phase, respectively. The changes in replication rate occur mainly through changes in fork speed without affecting the number of active forks. An increase in fork speed does not induce replication stress directly, but increases DNA damage over time causing cell cycle arrest. Thus, E2F-dependent transcription determines the DNA replication capacity of a cell, which affects the replication rate, controlling the time it takes to duplicate the genome and complete S-phase. Nature Publishing Group UK 2020-07-14 /pmc/articles/PMC7360579/ /pubmed/32665547 http://dx.doi.org/10.1038/s41467-020-17146-z Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pennycook, Betheney R.
Vesela, Eva
Peripolli, Silvia
Singh, Tanya
Barr, Alexis R.
Bertoli, Cosetta
de Bruin, Robertus A. M.
E2F-dependent transcription determines replication capacity and S phase length
title E2F-dependent transcription determines replication capacity and S phase length
title_full E2F-dependent transcription determines replication capacity and S phase length
title_fullStr E2F-dependent transcription determines replication capacity and S phase length
title_full_unstemmed E2F-dependent transcription determines replication capacity and S phase length
title_short E2F-dependent transcription determines replication capacity and S phase length
title_sort e2f-dependent transcription determines replication capacity and s phase length
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360579/
https://www.ncbi.nlm.nih.gov/pubmed/32665547
http://dx.doi.org/10.1038/s41467-020-17146-z
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