The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Science. 2010 Mar 26;327(5973):1657-61. doi: 10.1126/science.1185100.
Shelterin is an essential telomeric protein complex that prevents DNA damage signaling and DNA repair at mammalian chromosome ends. Here we report on the role of the TRF2-interacting factor Rap1, a conserved shelterin subunit of unknown function. We removed Rap1 from mouse telomeres either through gene deletion or by replacing TRF2 with a mutant that does not bind Rap1. Rap1 was dispensable for the essential functions of TRF2--repression of ATM kinase signaling and nonhomologous end joining (NHEJ)--and mice lacking telomeric Rap1 were viable and fertile. However, Rap1 was critical for the repression of homology-directed repair (HDR), which can alter telomere length. The data reveal that HDR at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within shelterin.
端粒体蛋白复合体是一种重要的端粒蛋白复合物，可防止 DNA 损伤信号和 DNA 修复在哺乳动物染色体末端发生。在这里，我们报告了 TRF2 相互作用因子 Rap1 的作用，Rap1 是一种保守的端粒体亚基，其功能未知。我们通过基因缺失或用不与 Rap1 结合的突变体替换 TRF2 从鼠端粒上去除 Rap1。Rap1 对于 TRF2 的基本功能（抑制 ATM 激酶信号和非同源末端连接（NHEJ））是可有可无的，并且缺乏端粒 Rap1 的小鼠是有活力和可育的。然而，Rap1 对于抑制同源重组修复（HDR）至关重要，HDR 可以改变端粒的长度。这些数据表明，在没有 DNA 损伤焦点的情况下，端粒处的 HDR 可以发生，并强调了端粒体蛋白复合体内部的功能区隔化。
