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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/08942 |
| _version_ | 1811200185063178240 |
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| author | Nicola Manfrini Michela Clerici Maxime Wery Chiara Vittoria Colombo Marc Descrimes Antonin Morillon Fabrizio d'Adda di Fagagna Maria Pia Longhese |
| author_facet | Nicola Manfrini Michela Clerici Maxime Wery Chiara Vittoria Colombo Marc Descrimes Antonin Morillon Fabrizio d'Adda di Fagagna Maria Pia Longhese |
| author_sort | Nicola Manfrini |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:00:32Z |
| format | Article |
| id | doaj.art-a299f99c985c4aaeb20cb74120be2584 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:00:32Z |
| publishDate | 2015-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a299f99c985c4aaeb20cb74120be25842022-12-22T03:52:41ZengeLife Sciences Publications LtdeLife2050-084X2015-07-01410.7554/eLife.08942Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiaeNicola Manfrini0Michela Clerici1Maxime Wery2Chiara Vittoria Colombo3Marc Descrimes4Antonin Morillon5Fabrizio d'Adda di Fagagna6Maria Pia Longhese7Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, ItalyDipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, ItalyInstitut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, FranceDipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, ItalyInstitut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, FranceInstitut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, FranceIFOM Foundation, FIRC Institute of Molecular Oncology Foundation, Milan, Italy; Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, ItalyDipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, ItalyEmerging 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.https://elifesciences.org/articles/08942DNA double-strand breakresectionS. cerevisiaetranscriptionRNA polymerase |
| spellingShingle | Nicola Manfrini Michela Clerici Maxime Wery Chiara Vittoria Colombo Marc Descrimes Antonin Morillon Fabrizio d'Adda di Fagagna Maria Pia Longhese Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae eLife DNA double-strand break resection S. cerevisiae transcription RNA polymerase |
| 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 | DNA double-strand break resection S. cerevisiae transcription RNA polymerase |
| url | https://elifesciences.org/articles/08942 |
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