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Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae
Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes indepe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541074/ https://www.ncbi.nlm.nih.gov/pubmed/26231041 http://dx.doi.org/10.7554/eLife.08942 |
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author | Manfrini, Nicola Clerici, Michela Wery, Maxime Colombo, Chiara Vittoria Descrimes, Marc Morillon, Antonin d'Adda di Fagagna, Fabrizio Longhese, Maria Pia |
author_facet | Manfrini, Nicola Clerici, Michela Wery, Maxime Colombo, Chiara Vittoria Descrimes, Marc Morillon, Antonin d'Adda di Fagagna, Fabrizio Longhese, Maria Pia |
author_sort | Manfrini, Nicola |
collection | PubMed |
description | Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. Since the DSB ends undergo nucleolytic degradation (resection) of their 5′-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. We discovered that resection-defective mutants fail to stop transcription around a DSB, and the extent of this failure correlates with the severity of the resection defect. Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. Therefore, the conversion of the DSB ends from double-stranded to single-stranded DNA, which is necessary to initiate DSB repair by homologous recombination, is responsible for loss of transcription around a DSB in S. cerevisiae. DOI: http://dx.doi.org/10.7554/eLife.08942.001 |
format | Online Article Text |
id | pubmed-4541074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45410742015-08-25 Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae Manfrini, Nicola Clerici, Michela Wery, Maxime Colombo, Chiara Vittoria Descrimes, Marc Morillon, Antonin d'Adda di Fagagna, Fabrizio Longhese, Maria Pia eLife Genes and Chromosomes Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. Since the DSB ends undergo nucleolytic degradation (resection) of their 5′-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. We discovered that resection-defective mutants fail to stop transcription around a DSB, and the extent of this failure correlates with the severity of the resection defect. Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. Therefore, the conversion of the DSB ends from double-stranded to single-stranded DNA, which is necessary to initiate DSB repair by homologous recombination, is responsible for loss of transcription around a DSB in S. cerevisiae. DOI: http://dx.doi.org/10.7554/eLife.08942.001 eLife Sciences Publications, Ltd 2015-07-31 /pmc/articles/PMC4541074/ /pubmed/26231041 http://dx.doi.org/10.7554/eLife.08942 Text en © 2015, Manfrini et al 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 Manfrini, Nicola Clerici, Michela Wery, Maxime Colombo, Chiara Vittoria Descrimes, Marc Morillon, Antonin d'Adda di Fagagna, Fabrizio Longhese, Maria Pia Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title | Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title_full | Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title_fullStr | Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title_full_unstemmed | Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title_short | Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae |
title_sort | resection is responsible for loss of transcription around a double-strand break in saccharomyces cerevisiae |
topic | Genes and Chromosomes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541074/ https://www.ncbi.nlm.nih.gov/pubmed/26231041 http://dx.doi.org/10.7554/eLife.08942 |
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