Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae

Nicola Manfrini (1) , Michela Clerici (1) , Maxime Wery (2, 3) , Chiara Vittoria Colombo (1) , Marc Descrimes (3, 2) , Antonin Morillon (3, 2) , Fabrizio d'Adda Du Fagagna (4, 5) , Maria Pia Longhese (1)

1 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 Dynamics of genetic information : fundamental basis and cancer
4 FIRC
5 CNR - National Research Council of Italy | Consiglio Nazionale delle Ricerche

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.

Domaines: Cancer

Nicola Manfrini, Michela Clerici, Maxime Wery, Chiara Vittoria Colombo, Marc Descrimes, et al.. Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae. eLife, 2015, 4, pp.e08942. ⟨10.7554/eLife.08942⟩. ⟨hal-01310355⟩