We found that in the absence of exogenous DNA damage, Jab1/CSN5-deficient embryos and osteosarcoma cells showed increased incidence of a spontaneous genome instability phenotype: findings included a large number of TUNEL foci in Jab1/CSN5-null embryos embryos and blastocysts and an increased number of γ-H2AX foci with a decreased percentage of intact DNA in Jab1/CSN5-deficient mouse embryonic fibroblasts and in human osteosarcoma cells [71]. The gene discussed is COPS5; the disease is osteosarcoma.