Lydall David
School of Biological Sciences, University of Manchester, G38 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
J Cell Sci. 2003 Oct 15;116(Pt 20):4057-65. doi: 10.1242/jcs.00765.
Telomeres stabilise DNA at the ends of chromosomes, preventing chromosome fusion and genetic instability. Telomeres differ from double strand breaks in that they activate neither DNA repair nor DNA damage checkpoint pathways. Paradoxically DNA repair and checkpoint genes play critical roles in telomere stability. Recent work has provided insights into the roles of DNA repair and DNA damage checkpoint pathways in the physiological maintenance of telomeres and in cellular responses when telomeres become uncapped. In budding yeast the Mre11p nuclease, along with other unidentified nucleases, plays critical roles in physiological telomere maintenance. However, when telomeres are uncapped, the 5'-to-3' exonuclease, Exo1p, plays a critical role in generating single-stranded DNA and activating checkpoint pathways. Intriguingly Exo1p does not play an important role in normal telomere maintenance. Although checkpoint pathways are not normally activated by telomeres, at least four different types of telomere defect activate checkpoint pathways. Interestingly, each of these telomere defects depends on a different subset of checkpoint proteins to induce cell cycle arrest. A model for how a spectrum of telomeric states might interact with telomerase and checkpoint pathways is proposed.
端粒可稳定染色体末端的DNA，防止染色体融合和遗传不稳定。端粒与双链断裂不同，因为它们既不激活DNA修复途径，也不激活DNA损伤检查点途径。矛盾的是，DNA修复基因和检查点基因在端粒稳定性中起着关键作用。最近的研究工作深入探讨了DNA修复和DNA损伤检查点途径在端粒生理维持以及端粒解帽时细胞反应中的作用。在芽殖酵母中，Mre11p核酸酶与其他未鉴定的核酸酶一起，在端粒的生理维持中起着关键作用。然而，当端粒解帽时，5'至3'核酸外切酶Exo1p在生成单链DNA和激活检查点途径中起着关键作用。有趣的是，Exo1p在正常端粒维持中并不起重要作用。虽然检查点途径通常不会被端粒激活，但至少有四种不同类型的端粒缺陷会激活检查点途径。有趣的是，这些端粒缺陷中的每一种都依赖于不同的检查点蛋白亚群来诱导细胞周期停滞。本文提出了一个关于一系列端粒状态如何与端粒酶和检查点途径相互作用的模型。
