Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae
- National Institute of Molecular Genetics Romeo ed Enrica Invernizzi"", Italy
- Università di Milano-Bicocca, Italy
- Université Pierre et Marie Curie, France
- FIRC Institute of Molecular Oncology Foundation, Italy
Abstract
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.
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© 2015, Manfrini et al.
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Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae
eLife 4:e08942.
https://doi.org/10.7554/eLife.08942
