端粒位于染色体末端，对于维持基因组的完整性以及染色体的稳定性有着重要的作用。端粒DNA主要由端粒酶负责延伸，如果细胞中没有端粒酶，随着细胞不断分裂，端粒DNA长度逐渐缩短，最终导致细胞衰老死亡。
1月24日，《自然·结构和分子生物学》（Nature Structural & Molecular Biology）在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所周金秋研究组的研究工作：端粒酶调控亚基Est1可以促进端粒单链DNA形成G4链高级结构，并且该活性对于体内端粒酶活性是必需的。这一发现阐释了Est1调控端粒酶活性的分子机理。该项工作主要由博士研究生张明亮和童夏静完成。
以前人们一直认为端粒G4链高级结构的形成对于端粒酶起着抑制的作用，因而一些抗肿瘤的先导化合物都是以促进或稳定G4链高级结构为出发点而进行筛选和相关临床试验。该发现对于以促进或稳定G4链高级结构为出发点筛选药物的策略提出了疑问。（生物谷Bioon.com）
周金秋研究员：端粒——稳定线性染色体的末端结构
生物谷推荐原始出处：
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.
