Mec1ATR is needed for extensive telomere elongation in response to ethanol in yeast.

Abstract

Telomere length homeostasis is essential for cell survival. In humans, telomeres shorten as a function of age. Short telomeres are known determinants of cell senescence and longevity. The yeast Saccharomyces cerevisiae expresses telomerase and maintains a strict telomere length homeostasis during vegetative growth. We have previously reported that different environmental signals promote changes in telomere length in S. cerevisiae. In particular, exposure to ethanol induces an extensive telomere elongation response due to a reduction in RAP1 mRNA and protein levels. Here we show that the reduction in Rap1 protein levels disrupts the physical interaction between Rap1 and Rif1, which in turn reduces the recruitment of these two proteins to telomeres during G2-phase. Although elongation of the shortest telomeres has been shown to depend on the Rif2 telomeric protein and on the Tel1(ATM) protein kinase, we show here that the extensive telomere elongation in response to ethanol exposure is Rif1 and Mec1 (ATR)-dependent. Our results fit a model in which Rif1 and Rap1 form a complex that is loaded onto telomeres at the end of S-phase. Reduced levels of the Rap1-Rif1 complex in ethanol lead to continuous telomere elongation in a Mec1-dependent process.