Question

求英文翻译

Next, we addressed the question of which step in the DDR response is inhibited by TRF2 by testing the localization of MDC1, RNF8 and RNF168 DNA-damage factors that are downstream of γH2AX and upstream of 53BP1 (ref. 12). Upon TRF2 depletion, γH2AX, MDC1 and RNF8 localize to telomeres in cells expressing TRFcT, confirming that the TRF2 TRFH domain is required to prevent the initial steps in the DDR pathway (Fig. 2a, b, d). Similarly, we did not detect defects in SUMO1 accumulation at telomeres (data not shown). By contrast, the ubiquitin ligase RNF168 does not localize to TRFcT-bound telomeres (Fig. 2c, d). We exclude the possibility that this is due to a general inhibition of RNF168 activity in these cells as they readily form RNF168 irradiation-induced foci (Supplementary Fig. 9). Recruitment of RNF168 at sites of damage is required for efficient 53BP1 recruitment3, 13, which in turn promotes chromosome fusions11.
To identify the critical region of TRF2 involved in the suppression of RNF168 recruitment, we focused on the hinge domain, given the high frequency of 53BP1 TIFs observed in cells expressing TRFcH (Fig. 1d). The main function attributed to this domain until now has been the interaction with RAP1 and TIN2 (also known as TERF2IP and TINF2, respectively), two members of the shelterin complex that have been implicated in end protection14, 15, 16.

Answer 1

接下来，我们解决的问题，这在DDR反应步骤由TRF2通过测试MDC1本地化的抑制，RNF8与RNF168 DNA损伤因子是γH2AX的上游和下游53BP1（参考文献12）。在TRF2耗尽，γH2AX，MDC1和蛋白定位于细胞表达trfct端粒，证实TRF2 TRFH域必须防止在DDR通路的初始步骤（图2A，B，D）。同样地，我们没有在端粒检测SUMO1积累缺陷（数据未显示）。相比之下，泛素连接酶RNF168不定位于trfct绑定的端粒（图2C，D）。我们排除了，这是由于在这些细胞中的活性抑制RNF168一般他们很容易形成辐射诱导灶RNF168的可能性（补充图9）。在损伤部位的RNF168招聘是有效的53BP1招聘3，13的要求，从而促进染色体fusions11
确定TRF2参与RNF168招聘抑制临界区，我们集中在铰链区，由于在细胞中表达trfch 53BP1 TIF观察到的高频率（图1d）。主要功能归因于这一领域至今已与Rap1，TIN2的相互作用（也被称为terf2ip、TINF2，分别），的shelterin复杂有牵连的端protection14，15的两个成员，16。

Answer 2

接下来,我们解决问题的步骤在DDR反应抑制了TRF2通过测试的本土化,RNF8和RNF168 MDC1 dna损伤因素的下游和上游的γH2AX 53 bp1(ref。12)。在TRF2损耗,γH2AX,MDC1和RNF8定位到染色体端粒在细胞表达TRFcT,确认TRFH TRF2域必须防止初始步骤在DDR途径(图2 a,b,d)。同样,我们没有检测缺陷在端粒SUMO1积累(数据未sh