Rif1/2 and Tel1 function in separate pathways during replicative senescence.

摘要

Telomeres, the physical ends of linear eukaryotic chromosomes, are bound by proteins that protect chromosome ends from being recognized as DNA double-stranded breaks. Telomeres shorten due to incomplete DNA replication and nucleolytic degradation. This shortening is counteracted by a specialized reverse transcriptase called telomerase. In the budding yeast Saccharornyces cerevisiae, deletion of any of the genes encoding telomerase components-such as the EST2 gene, which encodes the protein catalytic subunit-leads to an ever (Shorter telomere (EST) phenotype and replicative senescence within 60—80 generations. Rare cells can escape senescence to become survivors, maintaining their telomeres via DNA recombination.There are many genes involved in the regulation of telomere length homeo-stasis, including the phosphoinositide-3-kinase-related kinases Tell and Mecl, yeast orthologs of human ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related), respectively. Yeast cells lacking Tell have short but stable telomeres, while mutation of MEC1 confers a mild telomere shortening phenotype.