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The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae

In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by Ku, a ring-shaped protein heterodimer best known for its function in DNA repair. Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase recruitment to telomeres, but how this is achieved remain...

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Detalles Bibliográficos
Autores principales: Hass, Evan P, Zappulla, David C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547093/
https://www.ncbi.nlm.nih.gov/pubmed/26218225
http://dx.doi.org/10.7554/eLife.07750
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author Hass, Evan P
Zappulla, David C
author_facet Hass, Evan P
Zappulla, David C
author_sort Hass, Evan P
collection PubMed
description In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by Ku, a ring-shaped protein heterodimer best known for its function in DNA repair. Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase recruitment to telomeres, but how this is achieved remains unknown. Using telomere-length analysis and chromatin immunoprecipitation, we show that Sir4 – a previously identified Ku-binding protein that is a component of telomeric silent chromatin – is required for Ku-mediated telomere lengthening and telomerase recruitment. We also find that specifically tethering Sir4 directly to Ku-binding-defective telomerase RNA restores otherwise-shortened telomeres to wild-type length. These findings suggest that Sir4 is the telomere-bound target of Ku-mediated telomerase recruitment and provide one mechanism for how the Sir4-competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast. DOI: http://dx.doi.org/10.7554/eLife.07750.001
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spelling pubmed-45470932015-08-25 The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae Hass, Evan P Zappulla, David C eLife Genes and Chromosomes In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by Ku, a ring-shaped protein heterodimer best known for its function in DNA repair. Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase recruitment to telomeres, but how this is achieved remains unknown. Using telomere-length analysis and chromatin immunoprecipitation, we show that Sir4 – a previously identified Ku-binding protein that is a component of telomeric silent chromatin – is required for Ku-mediated telomere lengthening and telomerase recruitment. We also find that specifically tethering Sir4 directly to Ku-binding-defective telomerase RNA restores otherwise-shortened telomeres to wild-type length. These findings suggest that Sir4 is the telomere-bound target of Ku-mediated telomerase recruitment and provide one mechanism for how the Sir4-competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast. DOI: http://dx.doi.org/10.7554/eLife.07750.001 eLife Sciences Publications, Ltd 2015-07-28 /pmc/articles/PMC4547093/ /pubmed/26218225 http://dx.doi.org/10.7554/eLife.07750 Text en © 2015, Hass and Zappulla http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genes and Chromosomes
Hass, Evan P
Zappulla, David C
The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title_full The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title_fullStr The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title_full_unstemmed The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title_short The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae
title_sort ku subunit of telomerase binds sir4 to recruit telomerase to lengthen telomeres in s. cerevisiae
topic Genes and Chromosomes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547093/
https://www.ncbi.nlm.nih.gov/pubmed/26218225
http://dx.doi.org/10.7554/eLife.07750
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