Considering that disease-associated mutations in RTEL1 previously associated with dyskeratosis congenita/Hoyeraal-Hreidarsson syndrome are scattered throughout the tertiary structure of RTEL1, including some in the helicase domain, we asked whether any of these mutations might disrupt the integrity of the emerging RTEL1–Poldip3 complex (Supplemental Fig. S2A). Here, RTEL1 is linked to Hoyeraal-Hreidarsson syndrome.