Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae

In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetit ive sequence [poly(TG(1-3))] 350 to 500 bp in length. Strains with a mutati on of TEL1, a homolog of the human gene (ATM) mutated in patients with atax ia telangiectasia, have short but stable telomeric repeats. Mutations of TL C1 (encoding the RNA subunit of telomerase) result in strains that have con tinually shortening telomeres and a gradual loss of cell viability; survivo rs of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mut ation in MEC1 (a gene related in sequence to TEL1 and ATM) reduces telomere length and that tel1 mec1 double mutant strains have a senescent phenotype similar to that found in tlc1 strains. As observed in tlc1 strains, surviv ors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent ampl ification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 and tlc1 mutations have a delayed loss of cell viabi lity compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activ ation of telomerase.