端粒是位于真核生物線性染色體末端的由DNA和蛋白質(zhì)組成的復合物結(jié)構(gòu),，它對于基因組的完整性以及染色體的穩(wěn)定性發(fā)揮著至關重要的作用,，端粒DNA長度以及其結(jié)構(gòu)的維持與細胞衰老和癌癥發(fā)生密切相關。在有端粒酶活性的細胞中,，端粒酶途徑是端粒DNA長度維持的主要機制；當端粒酶缺失時,，細胞也可以通過同源重組途徑維持端粒DNA長度,。
在釀酒酵母中，端粒酶全酶包括催化亞基Est2,，RNA模版亞基Tlc1,，以及調(diào)控亞基Est1和Est3。上海生科院生化與細胞所周金秋研究組發(fā)現(xiàn),，Est1可以促進端粒單鏈DNA形成G4鏈高級結(jié)構(gòu)，并且該活性對于端粒的復制是必需的,，該研究成果發(fā)表在Nature Structural & Molecular Biology期刊上,。延續(xù)研究發(fā)現(xiàn)，Est1通過促進端粒G4鏈高級結(jié)構(gòu)的形成而參與端粒末端保護,，抑制端粒DNA發(fā)生同源重組,。這一研究成果于1月10日在Molecular and Cellular Biology上在線發(fā)表。由童夏靜等人完成的這些研究提出了Est1調(diào)控端粒酶活性及保護端粒的新模型,，即Est1通過促進端粒DNA形成G4鏈高級結(jié)構(gòu),，發(fā)揮著激活端粒酶以及保護端粒的雙重功能。
該工作得到了國家自然科學基金委和科技部的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
