In summary, our study reveals that tumor borne alleles (rad50-D67N/Y, rad50-R1259C, mre11-E38K, and rad50-L1240F) found in 25 distinct tumors (Fig 1A) exhibit separation of function phenotypes specifically impairing Tel1 activation, while only partially affecting DSB repair. This evidence concerns the gene MRE11 and neoplasm.