Bailey Susan M
Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523-1618, USA.
Radiat Res. 2008 Jan;169(1):1-7. doi: 10.1667/RR1197.1.
Bailey, S. Telomeres and Double-Strand Breaks - All's Well that "Ends" Well. ... Radiat. Res. 169, 1-7 (2008). Sometimes one's life (including one's science) makes a lot more sense when viewed from the perspective of time, reflected back on over a number of years. That has indeed been the case for me. Strangely enough, the story begins with chromosomes and "ends" with telomeres, both at Colorado State University. And, just as with chromosomes, a lot happened in between. Telomeres were first identified based on their function-they protected the physical ends of chromosomes from interaction with broken DNA ends created by ionizing radiation. While I was at Los Alamos National Laboratory, the sequence of human telomeres was discovered, making probes available that allowed us to re-examine and provide direct support of these early observations; thus began my fascination with telomeres. Chromosome orientation in situ hybridization (CO-FISH) also came onto the scene while I was in Los Alamos. This strand-specific modification of standard FISH, especially when combined with telomeric sequence probes, has proven to be a powerful approach that provides information not available by any other means. Applications have included pericentric inversion detection, distinction between leading- and lagging-strand telomeres, and identification of telomere-double-strand break (DSB) fusions. We also provided the first direct evidence that DSB repair proteins (DNA-PK in particular) are required for mammalian telomeric end capping, and we have been characterizing telomere dysfunction in NHEJ and HR repair-deficient backgrounds ever since. Cells must correctly distinguish between DNA ends represented by telomeres and DNA ends produced by DSBs if all is to end well. Just as these studies have provided new insight into the complex, often surprising, interactions at DNA ends, they also provoke new questions. Whereas it is now well established that DSB repair proteins associate with telomeres, most recently we've been asking whether the reverse scenario holds: Do telomere proteins interact with DSBs? We find that DSBs induced by ionizing radiations are not sufficient to recruit the essential telomere protein TRF2 as an early damage response, so perhaps this interplay is a one-way street. The rest of the story waits to unfold.
贝利，S. 端粒与双链断裂——结局好就一切都好。……《辐射研究》169卷，第1 - 7页（2008年）。有时候，当从时间的角度回顾多年来的经历时，一个人的生活（包括其科学研究）会更有意义。对我来说确实如此。说来也怪，这个故事始于科罗拉多州立大学的染色体，“终结”于端粒。而且，就像染色体一样，其间发生了很多事情。端粒最初是根据其功能被识别出来的——它们保护染色体的物理末端，使其免受电离辐射产生的断裂DNA末端的相互作用影响。我在洛斯阿拉莫斯国家实验室期间，人类端粒的序列被发现了，这使得探针得以问世，让我们能够重新审视并为这些早期观察提供直接支持；于是我开始对端粒着迷。染色体原位杂交（CO - FISH）也是在我在洛斯阿拉莫斯期间出现的。这种对标准FISH的链特异性修饰，尤其是与端粒序列探针结合时，已被证明是一种强大的方法，能提供其他任何方法都无法获得的信息。其应用包括着丝粒倒位检测、前导链和后随链端粒的区分以及端粒 - 双链断裂（DSB）融合的鉴定。我们还提供了首个直接证据，证明哺乳动物端粒末端封端需要DSB修复蛋白（特别是DNA - PK），从那时起我们一直在研究非同源末端连接（NHEJ）和同源重组（HR）修复缺陷背景下的端粒功能障碍。如果一切都要有个好结局，细胞必须正确区分端粒所代表的DNA末端和DSB产生的DNA末端。正如这些研究为DNA末端复杂且常常令人惊讶的相互作用提供了新的见解一样，它们也引发了新的问题。虽然现在已经明确DSB修复蛋白与端粒相关联，但最近我们一直在问相反的情况是否成立：端粒蛋白是否与DSB相互作用？我们发现电离辐射诱导的DSB不足以招募关键的端粒蛋白TRF2作为早期损伤反应，所以也许这种相互作用是单向的。故事的其余部分有待展开。
