The Francis Crick Institute, London NW1 1AT, United Kingdom.
Genes Dev. 2021 Jan 1;35(1-2):1-21. doi: 10.1101/gad.344044.120. Epub 2020 Dec 23.
In this perspective, we introduce shelterin and the mechanisms of ATM activation and NHEJ at telomeres, before discussing the following questions: How are t-loops proposed to protect chromosome ends and what is the evidence for this model? Can other models explain how TRF2 mediates end protection? Could t-loops be pathological structures? How is end protection achieved in pluripotent cells? What do the insights into telomere end protection in pluripotent cells mean for the t-loop model of end protection? Why might different cell states have evolved different mechanisms of end protection? Finally, we offer support for an updated t-loop model of end protection, suggesting that the data is supportive of a critical role for t-loops in protecting chromosome ends from NHEJ and ATM activation, but that other mechanisms are involved. Finally, we propose that t-loops are likely dynamic, rather than static, structures.
在这篇观点文章中，我们介绍了庇护体，以及 ATM 在端粒处激活和 NHEJ 的机制，然后讨论了以下问题：t 环如何被提出以保护染色体末端，以及该模型的证据是什么？其他模型能否解释 TRF2 如何介导末端保护？t 环可能是病理性结构吗？多能细胞中如何实现末端保护？多能细胞中端粒末端保护的见解对端粒末端保护的 t 环模型意味着什么？为什么不同的细胞状态可能进化出不同的末端保护机制？最后，我们为更新的端粒末端保护 t 环模型提供了支持，表明数据支持 t 环在保护染色体末端免受 NHEJ 和 ATM 激活方面的关键作用，但也涉及其他机制。最后，我们提出 t 环可能是动态的，而不是静态的结构。
