Abstract
Previous models suggested that regulation of telomere length in Saccharomyces cerevisiae by Tel1(ATM) and Mec1(ATR) would parallel the established pathways regulating the DNA damage response. Here, we provide evidence that telomere length regulation differs from the DNA damage response in both the Tel1 and Mec1 pathways. We found that Rad53 mediates a Mec1 telomere length regulation pathway but is dispensable for Tel1 telomere length regulation, whereas in the DNA damage response, Rad53 is regulated by both Mec1 and Tel1 Using epistasis analysis with a Tel1 hypermorphic allele, Tel1-hy909, we found that the MRX complex is not required downstream of Tel1 for telomere elongation but is required downstream of Tel1 for the DNA damage response. Our data suggest that nucleolytic telomere end processing is not a required step for telomerase to elongate telomeres.
Highlights
Previous models suggested that regulation of telomere length in Saccharomyces cerevisiae by Tel1(ATM) and Mec1(ATR) would parallel the established pathways regulating the DNA damage response
Telomere elongation and DNA damage response are regulated through different mechanisms We found that, in contrast to published models, the MRX complex is not required after Tel1 activation for telomere elongation
Our data suggest a new model in which Tel1 activation by MRX is sufficient for telomere length regulation but not for the DNA damage response (Figure 6)
Summary
Previous models suggested that regulation of telomere length in Saccharomyces cerevisiae by Tel1(ATM) and Mec1(ATR) would parallel the established pathways regulating the DNA damage response. The distinct effects of tel1D and mec1D on telomere length and the DNA damage response suggest Tel and Mec may have different critical substrates Both Tel and Mec phosphorylate proteins on serines and threonines at S/T-Q motifs (Kim et al 1999). We investigated the role of two known substrates, Rad and the Mre11-Rad50-Xrs (MRX) complex, which have been shown to be phosphorylated by Tel and/or Mec in response to DNA damage (D’Amours and Jackson 2001; Nakada et al 2003b; Smolka et al 2007; Albuquerque et al 2008; Bastos de Oliveira et al 2015; Lavin et al 2015). Several studies have suggested that similar regulatory events occur at telomeres (Nugent et al 1998; Tsukamoto et al 2001; Larrivee et al 2004; Viscardi et al 2007; Bonetti et al 2009), specific mechanisms are not well established
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