The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Mol Cell Biol. 2011 Mar;31(6):1263-74. doi: 10.1128/MCB.00831-10. Epub 2011 Jan 10.
In the budding yeast Saccharomyces cerevisiae, the structure and function of telomeres are maintained by binding proteins, such as Cdc13-Stn1-Ten1 (CST), Yku, and the telomerase complex. Like CST and Yku, telomerase also plays a role in telomere protection or capping. Unlike CST and Yku, however, the underlying molecular mechanism of telomerase-mediated telomere protection remains unclear. In this study, we employed both the CDC13-EST1 fusion gene and the separation-of-function allele est1-D514A to elucidate that Est1 provided a telomere protection pathway that was independent of both the CST and Yku pathways. Est1's ability to convert single-stranded telomeric DNA into a G quadruplex was required for telomerase-mediated telomere protection function. Additionally, Est1 maintained the integrity of telomeres by suppressing the recombination of subtelomeric Y' elements. Our results demonstrate that one major functional role that Est1 brings to the telomerase complex is the capping or protection of telomeres.
在 budding 酵母酿酒酵母中,端粒的结构和功能通过结合蛋白来维持,如 Cdc13-Stn1-Ten1(CST)、Yku 和端粒酶复合物。与 CST 和 Yku 一样,端粒酶在端粒保护或封端中也发挥作用。然而,与 CST 和 Yku 不同的是,端粒酶介导的端粒保护的潜在分子机制尚不清楚。在这项研究中,我们同时使用了 CDC13-EST1 融合基因和分离功能等位基因 est1-D514A,以阐明 Est1 提供了一种独立于 CST 和 Yku 途径的端粒保护途径。Est1 将单链端粒 DNA 转化为 G 四联体的能力对于端粒酶介导的端粒保护功能是必需的。此外,Est1 通过抑制亚端粒 Y' 元件的重组来维持端粒的完整性。我们的结果表明,Est1 为端粒酶复合物带来的主要功能之一是端粒的封端或保护。