FBXW7 facilitates NHEJ in a degradation-independent manner via K63-linked polyubiquitination of X-ray repair cross-complementing protein 4 (XRCC4) at lysine 286, implying that inactivating FBXW7 could be a potential strategy for improving the efficacy of radiotherapy in human cancers [141]. Here, XRCC4 is linked to cancer.