Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage

Abstract Background The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells. Results By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding y...

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Autores principales:	Satyaprakash Pandey, Mona Hajikazemi, Theresa Zacheja, Stephanie Schalbetter, Jonathan Baxter, Victor Guryev, Andreas Hofmann, Dieter W. Heermann, Stefan A. Juranek, Katrin Paeschke
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	DNA damage Genome stability Telomerase Yeast Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/49015b42ea7c44bda95a827b3a9a2668
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spelling	oai:doaj.org-article:49015b42ea7c44bda95a827b3a9a26682021-11-21T12:42:18ZTelomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage10.1186/s12915-021-01167-11741-7007https://doaj.org/article/49015b42ea7c44bda95a827b3a9a26682021-11-01T00:00:00Zhttps://doi.org/10.1186/s12915-021-01167-1https://doaj.org/toc/1741-7007Abstract Background The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells. Results By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability. Conclusions Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition.Satyaprakash PandeyMona HajikazemiTheresa ZachejaStephanie SchalbetterJonathan BaxterVictor GuryevAndreas HofmannDieter W. HeermannStefan A. JuranekKatrin PaeschkeBMCarticleDNA damageGenome stabilityTelomeraseYeastBiology (General)QH301-705.5ENBMC Biology, Vol 19, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA damage Genome stability Telomerase Yeast Biology (General) QH301-705.5
spellingShingle	DNA damage Genome stability Telomerase Yeast Biology (General) QH301-705.5 Satyaprakash Pandey Mona Hajikazemi Theresa Zacheja Stephanie Schalbetter Jonathan Baxter Victor Guryev Andreas Hofmann Dieter W. Heermann Stefan A. Juranek Katrin Paeschke Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
description	Abstract Background The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells. Results By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability. Conclusions Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition.
format	article
author	Satyaprakash Pandey Mona Hajikazemi Theresa Zacheja Stephanie Schalbetter Jonathan Baxter Victor Guryev Andreas Hofmann Dieter W. Heermann Stefan A. Juranek Katrin Paeschke
author_facet	Satyaprakash Pandey Mona Hajikazemi Theresa Zacheja Stephanie Schalbetter Jonathan Baxter Victor Guryev Andreas Hofmann Dieter W. Heermann Stefan A. Juranek Katrin Paeschke
author_sort	Satyaprakash Pandey
title	Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
title_short	Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
title_full	Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
title_fullStr	Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
title_full_unstemmed	Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
title_sort	telomerase subunit est2 marks internal sites that are prone to accumulate dna damage
publisher	BMC
publishDate	2021
url	https://doaj.org/article/49015b42ea7c44bda95a827b3a9a2668
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Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage

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