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.

中文翻译：

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末端保护问题——尾部出乎意料的扭曲

从这个角度来看，在讨论以下问题之前，我们介绍了 Shelterin 以及 ATM 激活和 NHEJ 的机制，然后讨论了以下问题：如何提出 t 环来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 如何调节末端保护？T环可能是病理结构吗？如何在多能细胞中实现末端保护？对多能细胞端粒末端保护的见解对末端保护的 t 环模型意味着什么？为什么不同的细胞状态会进化出不同的末端保护机制？最后，我们支持更新的末端保护 t 环模型，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，但涉及其他机制。最后，