The DNA-dependent protein kinase (DNA-PK) is a central component of NHEJ [7, 8], and a highly potent and specific inhibitor of DNA-PK (NU7441; 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one) has been used successfully in in vitro and in vivo models to sensitize colon cancer cells and CLL blasts to the effects of DNA-damaging chemo- and/or radiotherapy [9, 10]. The gene discussed is PRKDC; the disease is B-cell chronic lymphocytic leukemia.