In line with an involvement of the RNF8-RNF168 pathway in hematopoiesis, inactivating mutations in RNF168 are associated with the RIDDLE syndrome, characterized by cellular radiosensitivity and immunodeficiency (Stewart et al., 2009), features which are recapitulated in knockout mouse models for these E3s (Li et al., 2010; Santos et al., 2010; Bohgaki et al., 2011). This evidence concerns the gene RNF168 and RIDDLE syndrome.