European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, The Netherlands.
G3 (Bethesda). 2023 May 2;13(5). doi: 10.1093/g3journal/jkad065.
In Saccharomyces cerevisiae, telomerase recruitment to telomeres depends on a direct interaction between Cdc13, a protein that binds single-stranded telomeric DNA, and the Est1 subunit of telomerase. The cdc13-2 allele disrupts telomerase association with telomeres, resulting in progressive telomere shortening and replicative senescence. The Mec1/ATR kinase is both a positive and a negative regulator of telomerase activity and is required for the cell cycle arrest in telomerase-deficient senescent cells. In this study, we find that the deletion of MEC1 suppresses the replicative senescence of cdc13-2. This suppression is dependent on telomerase, indicating that Mec1 antagonizes telomerase-mediated telomere extension in cdc13-2 cells to promote senescence.
在酿酒酵母中，端粒酶被招募到端粒上依赖于 Cdc13 蛋白与端粒酶的 Est1 亚基之间的直接相互作用，Cdc13 蛋白能结合单链端粒 DNA。cdc13-2 等位基因破坏了端粒酶与端粒的结合，导致端粒逐渐缩短和复制性衰老。Mec1/ATR 激酶是端粒酶活性的正向和负向调节剂，并且是端粒酶缺陷型衰老细胞中细胞周期停滞所必需的。在这项研究中，我们发现 MEC1 的缺失抑制了 cdc13-2 的复制性衰老。这种抑制依赖于端粒酶，表明 Mec1 拮抗端粒酶介导的 cdc13-2 细胞中端粒的延伸，以促进衰老。
