RAD50 and cancer: A fundamental difference between the human cancer cells and S. cerevisiae is that, while ScRev7 robustly interacts with and suppresses the biochemical activities of both Mre11 and Rad50 subunits to facilitate NHEJ, Rev7–Shieldin complex acts as a downstream effector of 53BP1-RIF1 in restraining DNA end resection to promote NHEJ (Clairmont and D’Andrea, 2021; Paniagua and Jacobs, 2023).