求英文翻译Next, we addressed the question of which step in the DD

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.