Suppression of cdc13-2-associated senescence by pif1-m2 requires Ku-mediated telomerase recruitment

• Published in: G3 : genes - genomes - genetics Vol. 12; no. 1
• Main Authors: Fekete-Szücs, Enikő, Rosas Bringas, Fernando R, Stinus, Sonia, Chang, Michael
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2022
• Subjects: DNA Helicases - genetics; DNA Helicases - metabolism; DNA-Binding Proteins; Investigation; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Telomerase - genetics; Telomerase - metabolism; Telomere - genetics; Telomere - metabolism; Telomere-Binding Proteins - genetics; Pif1; replicative senescence; telomerase recruitment; Cdc13; Ku complex
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1093/g3journal/jkab360

In Saccharomyces cerevisiae, recruitment of telomerase to telomeres requires an interaction between Cdc13, which binds single-stranded telomeric DNA, and the Est1 subunit of telomerase. A second pathway involving an interaction between the yKu complex and telomerase RNA (TLC1) contributes to telomerase recruitment but cannot sufficiently recruit telomerase on its own to prevent replicative senescence when the primary Cdc13-Est1 pathway is abolished-for example, in the cdc13-2 mutant. In this study, we find that mutation of PIF1, which encodes a helicase that inhibits telomerase, suppresses the replicative senescence of cdc13-2 by increasing reliance on the yKu-TLC1 pathway for telomerase recruitment. Our findings reveal new insight into telomerase-mediated telomere maintenance.