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.

Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae / N. Manfrini, M. Clerici, M. Wery, C.V. Colombo, M. Descrimes, A. Morillon, F. d'Adda di fagagna, M.P. Longhese. - In: ELIFE. - ISSN 2050-084X. - 4(2015 Jul), pp. e08942.1-e08942.15. [10.7554/eLife.08942]

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

N. Manfrini
Primo
;
2015-07

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.
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/18 - Genetica
Article (author)
File in questo prodotto:
File Dimensione Formato  
9_elife_2015.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 3.03 MB
Formato Adobe PDF
3.03 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/861032
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 23
social impact