title: Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae.
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.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Manfrini
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Wery
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
authors.forename: Chiara Vittoria
authors.initials: CV
authors.lastname: Colombo
authors.affiliation: Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Descrimes
authors.affiliation: Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Morillon
authors.affiliation: IFOM Foundation, FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: d'Adda di Fagagna
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Longhese
mesh_terms: D053903:DNA Breaks, Double-Stranded; D045643:DNA Repair Enzymes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D045643:DNA Repair Enzymes
keywords: DNA double-strand breaks; RNA polymerase; S. cerevisiae; chromosomes; genes; resection; transcription