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.

Manfrini, N., Clerici, M., Wery, M., Colombo, C., Descrimes, M., Morillon, A., et al. (2015). Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae. ELIFE, 4(2015), 1-15 [10.7554/eLife.08942].

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

Manfrini, N
Primo
;
CLERICI, MICHELA
Secondo
;
COLOMBO, CHIARA VITTORIA;LONGHESE, MARIA PIA
Ultimo
2015

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
DNA double-strand breaks; RNA polymerase; S. cerevisiae; chromosomes; genes; resection; transcription; Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all); Medicine (all); Neuroscience (all)
English
1
15
15
Manfrini, N., Clerici, M., Wery, M., Colombo, C., Descrimes, M., Morillon, A., et al. (2015). Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae. ELIFE, 4(2015), 1-15 [10.7554/eLife.08942].
Manfrini, N; Clerici, M; Wery, M; Colombo, C; Descrimes, M; Morillon, A; d’Adda di fagagna, F; Longhese, M
File in questo prodotto:
File Dimensione Formato  
3-Manfrini_2015_elife-08942-v2.pdf

Solo gestori archivio

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 3.03 MB
Formato Adobe PDF
3.03 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/10281/96027
Citazioni
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 23
Social impact