Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, HenryWellcome Laboratory, Newcastle University, Tyne and Wear, UK.
EMBO J. 2009 Aug 5;28(15):2174-87. doi: 10.1038/emboj.2009.176. Epub 2009 Jul 23.
Telomeres are by definition stable and inert chromosome ends, whereas internal chromosome breaks are potent stimulators of the DNA damage response (DDR). Telomeres do not, as might be expected, exclude DDR proteins from chromosome ends but instead engage with many DDR proteins. However, the most powerful DDRs, those that might induce chromosome fusion or cell-cycle arrest, are inhibited at telomeres. In budding yeast, many DDR proteins that accumulate most rapidly at double strand breaks (DSBs), have important functions in physiological telomere maintenance, whereas DDR proteins that arrive later tend to have less important functions. Considerable diversity in telomere structure has evolved in different organisms and, perhaps reflecting this diversity, different DDR proteins seem to have distinct roles in telomere physiology in different organisms. Drawing principally on studies in simple model organisms such as budding yeast, in which many fundamental aspects of the DDR and telomere biology have been established; current views on how telomeres harness aspects of DDR pathways to maintain telomere stability and permit cell-cycle division are discussed.
端粒从定义上讲是稳定且惰性的染色体末端,而内部染色体断裂是 DNA 损伤反应 (DDR) 的有力刺激物。端粒并没有像人们可能预期的那样将 DDR 蛋白排除在染色体末端之外,而是与许多 DDR 蛋白结合。然而,最强大的 DDR,那些可能诱导染色体融合或细胞周期停滞的 DDR,在端粒处受到抑制。在芽殖酵母中,许多在双链断裂 (DSB) 处积累最快的 DDR 蛋白在生理端粒维持中具有重要功能,而那些后来到达的 DDR 蛋白往往具有不太重要的功能。不同生物体中端粒结构的多样性已经进化,也许反映了这种多样性,不同的 DDR 蛋白在不同生物体的端粒生理学中似乎具有不同的作用。主要参考芽殖酵母等简单模式生物的研究,其中已经确立了 DDR 和端粒生物学的许多基本方面;讨论了端粒如何利用 DDR 途径的各个方面来维持端粒稳定性并允许细胞周期分裂的当前观点。