Our study demonstrated that RNF8 E3 ubiquitin-protein ligase, which is known to bind ATM-phosphorylated MDC1 to promote histone ubiquitylation nearby DSB lesions for promoting DSB repair signals [28], actually protects ATM-phosphorylated MDC1 from caspase-3-dependent cleavage in BIN1-deficient cancer cells, thereby sustaining cisplatin resistance. The gene discussed is CASP3; the disease is cancer.