The State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Elife. 2020 Aug 5;9:e53144. doi: 10.7554/eLife.53144.
Telomeres define the natural ends of eukaryotic chromosomes and are crucial for chromosomal stability. The budding yeast Cdc13, Stn1 and Ten1 proteins form a heterotrimeric complex, and the inactivation of any of its subunits leads to a uniformly lethal phenotype due to telomere deprotection. Although Cdc13, Stn1 and Ten1 seem to belong to an epistasis group, it remains unclear whether they function differently in telomere protection. Here, we employed the single-linear-chromosome yeast SY14, and surprisingly found that the deletion of leads to telomere erosion and intrachromosome end-to-end fusion, which depends on Rad52 but not Yku. Interestingly, the emergence frequency of survivors in the SY14 Δ mutant was ~29 fold higher than that in either the Δ or Δ mutant, demonstrating a predominant role of Cdc13 in inhibiting telomere fusion. Chromosomal fusion readily occurred in the telomerase-null SY14 strain, further verifying the default role of intact telomeres in inhibiting chromosome fusion.
端粒定义了真核染色体的自然末端,对染色体的稳定性至关重要。芽殖酵母 Cdc13、Stn1 和 Ten1 蛋白形成异源三聚体复合物,其任何亚基的失活都会导致端粒去保护,从而导致均匀致死表型。尽管 Cdc13、Stn1 和 Ten1 似乎属于上位群,但它们在端粒保护中的功能是否不同仍不清楚。在这里,我们利用单一线粒体酵母 SY14,令人惊讶的是发现删除导致端粒侵蚀和染色体内端到端融合,这依赖于 Rad52 但不依赖于 Yku。有趣的是,SY14Δ 突变体中存活者的出现频率比Δ或Δ突变体高约 29 倍,这表明 Cdc13 在抑制端粒融合中起主要作用。在端粒酶缺失的 SY14 菌株中,染色体融合很容易发生,进一步验证了完整端粒在抑制染色体融合中的默认作用。