Zubko Mikhajlo K, Lydall David
Institute for Ageing and Health, Henry Wellcome Laboratory for Biogerontology Research, University of Newcastle, Newcastle upon Tyne, NE4 6BE, UK.
Nat Cell Biol. 2006 Jul;8(7):734-40. doi: 10.1038/ncb1428. Epub 2006 Jun 11.
Telomeres were defined by their ability to cap chromosome ends. Proteins with high affinity for the structure at chromosome ends, binding the G-rich, 3' single-stranded overhang at telomeres include Pot1 in humans and fission yeast, TEBP in Oxytricha nova and Cdc13 in budding yeast. Cdc13 is considered essential for telomere capping because budding yeast that lack Cdc13 rapidly accumulate excessive single-stranded DNA (ssDNA) at telomeres, arrest cell division and die. Cdc13 has a separate, critical role in telomerase recruitment to telomeres. Here, we show that neither Cdc13 nor its partner Stn1 are necessary for telomere capping if nuclease activities that are active at uncapped telomeres are attenuated. Recombination-dependent and -independent mechanisms permit maintenance of chromosomes without Cdc13. Our results indicate that the structure of the eukaryotic telomere cap is remarkably flexible and that changes in the DNA damage response allow alternative strategies for telomere capping to evolve.
端粒是由其封闭染色体末端的能力所定义的。对染色体末端结构具有高亲和力、结合端粒富含G的3'单链突出端的蛋白质包括人类和裂殖酵母中的Pot1、新游仆虫中的TEBP以及芽殖酵母中的Cdc13。Cdc13被认为对端粒封闭至关重要，因为缺乏Cdc13的芽殖酵母会在端粒迅速积累过量的单链DNA（ssDNA），导致细胞分裂停滞并死亡。Cdc13在端粒酶招募至端粒过程中具有独立的关键作用。在此，我们表明，如果在未封闭端粒处活跃的核酸酶活性减弱，Cdc13及其伙伴Stn1对于端粒封闭都不是必需的。依赖重组和不依赖重组的机制使得在没有Cdc13的情况下染色体仍能得以维持。我们的结果表明，真核端粒帽的结构非常灵活，并且DNA损伤反应的变化允许端粒封闭的替代策略得以演化。
