van Overbeek Megan, de Lange Titia
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Curr Biol. 2006 Jul 11;16(13):1295-302. doi: 10.1016/j.cub.2006.05.022. Epub 2006 May 25.
Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.
人类染色体末端由端粒保护蛋白复合体（shelterin）保护，这是一种丰富的六亚基蛋白复合体，它能特异性结合端粒重复序列，调节端粒长度，并确保染色体末端不会引发DNA损伤反应（相关综述见）。通过对与端粒保护蛋白复合体成分Rap1相关的蛋白质进行质谱分析，我们鉴定出一种与Artemis密切相关的SMN1/PSO2核酸酶家族成员。我们将这种蛋白质称为Apollo，并报告称Apollo能够通过与端粒保护蛋白复合体成分TRF2相互作用而定位于端粒。尽管其在端粒处的丰度较低表明Apollo不是端粒保护蛋白复合体的核心成分，但用RNA干扰技术敲低Apollo会导致细胞衰老以及端粒处DNA损伤信号的激活，端粒功能障碍诱导灶（TIFs）就是证据。TIFs主要出现在S期，这表明Apollo有助于与染色体末端复制相关的一个加工步骤。此外，一些中期染色体在单染色单体末端显示出两个端粒信号，表明端粒结构异常。我们提出，类似Artemis的核酸酶Apollo是在端粒复制期间或之后保护端粒所需的一种端粒保护蛋白复合体辅助因子。
