端粒是位于真核生物线性染色体末端的由DNA和蛋白质组成的复合物结构，它对于基因组的完整性以及染色体的稳定性发挥着至关重要的作用，端粒DNA长度以及其结构的维持与细胞衰老和癌症发生密切相关。在有端粒酶活性的细胞中，端粒酶途径是端粒DNA长度维持的主要机制；当端粒酶缺失时，细胞也可以通过同源重组途径维持端粒DNA长度。
在酿酒酵母中，端粒酶全酶包括催化亚基Est2，RNA模版亚基Tlc1，以及调控亚基Est1和Est3。上海生科院生化与细胞所周金秋研究组发现，Est1可以促进端粒单链DNA形成G4链高级结构，并且该活性对于端粒的复制是必需的，该研究成果发表在Nature Structural & Molecular Biology期刊上。延续研究发现，Est1通过促进端粒G4链高级结构的形成而参与端粒末端保护，抑制端粒DNA发生同源重组。这一研究成果于1月10日在Molecular and Cellular Biology上在线发表。由童夏静等人完成的这些研究提出了Est1调控端粒酶活性及保护端粒的新模型，即Est1通过促进端粒DNA形成G4链高级结构，发挥着激活端粒酶以及保护端粒的双重功能。
该工作得到了国家自然科学基金委和科技部的资助。（生物谷Bioon.com）
生物谷推荐原文出处：
Mol. Cell. Biol. doi:10.1128/MCB.00831-10
Est1 protects telomeres and inhibits subtelomeric Y'-element recombination
Xia-Jing Tong, Qian-Jin Li, Yi-Min Duan, Ning-Ning Liu, Ming-Liang Zhang, and Jin-Qiu Zhou*
Abstract
In 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.
