ABSTRACT T-loops are thought to hide telomeres from DNA damage signaling and DSB repair pathways. T-loop formation requires the shelterin component TRF2, which represses ATM signaling and NHEJ. Here we establish that TRF2 alone, in the absence of other shelterin proteins can form t-loops. Mouse and human cells contain two isoforms of TRF2, one of which is uncharacterized. We show that both isoforms protect telomeres and form t-loops. The isoforms are not cell cycle regulated and t-loops are present in G1, S, and G2. Using the DNA wrapping deficient TRF2 Topless mutant, we confirm its inability to form t-loops and repress ATM. However, since the mutant is also defective in repression of NHEJ and telomeric localization, the role of topological changes in telomere protection remains unclear. Finally, we show that Rad51 does not affect t-loop frequencies or telomere protection. Therefore, alternative models for how TRF2 forms t-loops should be explored.

中文翻译：

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TRF2 对 t 环形成的表征

摘要 T 环被认为隐藏端粒免受 DNA 损伤信号和 DSB 修复途径的影响。T 环的形成需要 Shelterin 组件 TRF2，它抑制 ATM 信号和 NHEJ。在这里，我们确定单独的 TRF2 在没有其他保护蛋白的情况下可以形成 t 环。小鼠和人类细胞含有 TRF2 的两种同工型，其中一种是未鉴定的。我们表明这两种同工型都保护端粒并形成 t 环。同工型不受细胞周期调节，T 环存在于 G1、S 和 G2。使用 DNA 包裹缺陷 TRF2 Topless 突变体，我们确认其无法形成 t 环和抑制 ATM。然而，由于突变体在抑制 NHEJ 和端粒定位方面也存在缺陷，拓扑变化在端粒保护中的作用尚不清楚。最后，我们表明 Rad51 不影响 t 环频率或端粒保护。因此，应该探索 TRF2 如何形成 t 环的替代模型。