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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...

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Autores principales: Manfrini, Nicola, Clerici, Michela, Wery, Maxime, Colombo, Chiara Vittoria, Descrimes, Marc, Morillon, Antonin, d'Adda di Fagagna, Fabrizio, Longhese, Maria Pia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
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
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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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