In the present study, we identified three Ub-proteasome mutants exhibiting hypersensitivity to cisplatin, i.e., Ubp16, Ubc13 and Pmt3. Although with very distinct functions, the proteins encoded by those genes play critical roles for DNA damage response, thereby representing attractive targets to investigate possible mechanisms of cisplatin resistance in human tumor cell systems (Figure 2). Here, UBE2N is linked to neoplasm.