Interactions of TLC1 (Which Encodes the RNA Subunit of Telomerase), TEL1 , and MEC1 in Regulating Telomere Length in the Yeast Saccharomyces cerevisiae

Abstract

ABSTRACT In the yeast Saccharomyces cerevisiae , chromosomes terminate with a repetitive sequence [poly(TG 1–3 )] 350 to 500 bp in length. Strains with a mutation of TEL1 , a homolog of the human gene ( ATM ) mutated in patients with ataxia telangiectasia, have short but stable telomeric repeats. Mutations of TLC1 (encoding the RNA subunit of telomerase) result in strains that have continually shortening telomeres and a gradual loss of cell viability; survivors of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mutation 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, survivors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent amplification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 and tlc1 mutations have a delayed loss of cell viability compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activation of telomerase.