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Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double‐strand breaks
Author(s) -
Mantiero Davide,
Clerici Michela,
Lucchini Giovanna,
Longhese Maria Pia
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400911
Subject(s) - g2 m dna damage checkpoint , saccharomyces cerevisiae , microbiology and biotechnology , dna damage , biology , chek1 , dna , cell cycle checkpoint , genetics , yeast , cell cycle , gene
The main responder to DNA double‐strand breaks (DSBs) in mammals is ataxia telangiectasia mutated (ATM), whereas DSB‐induced checkpoint activation in budding yeast seems to depend primarily on the ATM and Rad‐3‐related (ATR) orthologue Mec1. Here, we show that Saccharomyces cerevisiae Tel1, the ATM orthologue, has two functions in checkpoint response to DSBs. First, Tel1 participates, together with the MRX complex, in Mec1‐dependent DSB‐induced checkpoint activation by increasing the efficiency of single‐stranded DNA accumulation at the ends of DSBs, and this checkpoint function can be overcome by overproducing the exonuclease Exo1. Second, Tel1 can activate the checkpoint response to DSBs independently of Mec1, although its signalling activity only becomes apparent when several DSBs are generated. Furthermore, we provide evidence that the kinetics of DSB resection can influence Tel1 activation, indicating that processing of the DSB termini might influence the transition from Tel1/ATM‐ to Mec1/ATR‐dependent checkpoint.