端粒位于染色體末端,，對于維持基因組的完整性以及染色體的穩(wěn)定性有著重要的作用。端粒DNA主要由端粒酶負(fù)責(zé)延伸,，如果細(xì)胞中沒有端粒酶,，隨著細(xì)胞不斷分裂，端粒DNA長度逐漸縮短,，最終導(dǎo)致細(xì)胞衰老死亡,。
1月24日，《自然·結(jié)構(gòu)和分子生物學(xué)》（Nature Structural & Molecular Biology）在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所周金秋研究組的研究工作：端粒酶調(diào)控亞基Est1可以促進(jìn)端粒單鏈DNA形成G4鏈高級結(jié)構(gòu),，并且該活性對于體內(nèi)端粒酶活性是必需的,。這一發(fā)現(xiàn)闡釋了Est1調(diào)控端粒酶活性的分子機理。該項工作主要由博士研究生張明亮和童夏靜完成,。
以前人們一直認(rèn)為端粒G4鏈高級結(jié)構(gòu)的形成對于端粒酶起著抑制的作用,，因而一些抗腫瘤的先導(dǎo)化合物都是以促進(jìn)或穩(wěn)定G4鏈高級結(jié)構(gòu)為出發(fā)點而進(jìn)行篩選和相關(guān)臨床試驗。該發(fā)現(xiàn)對于以促進(jìn)或穩(wěn)定G4鏈高級結(jié)構(gòu)為出發(fā)點篩選藥物的策略提出了疑問。（生物谷Bioon.com）
周金秋研究員：端粒——穩(wěn)定線性染色體的末端結(jié)構(gòu)
生物谷推薦原始出處：
Nature Structural & Molecular Biology 24 January 2010 | doi:10.1038/nsmb.1760
Yeast telomerase subunit Est1p has guanine quadruplex–promoting activity that is required for telomere elongation
Ming-Liang Zhang1,2, Xia-Jing Tong1,2, Xiao-Hong Fu1, Bo O Zhou1, Jianyong Wang1, Xin-Hua Liao1, Qian-Jin Li1, Ning Shen1, Jianping Ding1 & Jin-Qiu Zhou1
Telomeres are eukaryotic protein–DNA complexes found at the ends of linear chromosomes that are essential for maintaining genome integrity and are implicated in cellular aging and cancer. The guanine (G)-rich strand of telomeric DNA, usually elongated by the telomerase reverse transcriptase, can form a higher-order structure known as a G-quadruplex in vitro and in vivo. Several factors that promote or resolve G-quadruplexes have been identified, but the functional importance of these structures for telomere maintenance is not well understood. Here we show that the yeast telomerase subunit Est1p, known to be involved in telomerase recruitment to telomeres, can convert single-stranded telomeric G-rich DNA into a G-quadruplex structure in vitro in a Mg2+-dependent manner. Cells carrying Est1p mutants deficient in G-quadruplex formation in vitro showed gradual telomere shortening and cellular senescence, indicating a positive regulatory role for G-quadruplex in the maintenance of telomere length.
1 The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, Shanghai, China.
2 These authors contributed equally to this work.
