Our results reveal a mechanism to explain how the p97–ATX3–RNF8 complex fine‐tunes DSB repair by preventing excessive RNF8‐dependent K63‐Ub modifications and 5′‐DNA end resection and consequently promoting the NHEJ pathway, an essential pathway for cell survival after IR and thus cancer cell resistance to radiotherapy (Jeggo et al, 2011; Jeggo & Lobrich, 2015). This evidence concerns the gene ATXN3 and cancer.