DFFB (DNA fragmentation factor subunit beta) is a nuclease that executes apoptotic DNA fragmentation and chr1 condensation 1. As a caspase-activated DNase, DFFB cleaves chr1 DNA at specific sites, generating characteristic DNA end motifs detectable in cell-free DNA (cfDNA) 2. DFFB contributes to the fragmentomic landscape of plasma cfDNA, with distinct cleavage patterns that can be identified through analysis of 5' end sequences 2. The enzyme preferentially generates jagged DNA ends on mononucleosomal fragments, though less prominently than DNASE1L3 on multinucleosomal DNA 3. In long cfDNA molecules, DFFB activity is indicated by lower proportions of transcription start site-derived fragments compared to wild-type controls 4. Therapeutically, transgenic DFFB expression under targeted promoters (EGFR or POLA) enables selective elimination of cancer cells and undifferentiated stem cells while sparing healthy cells 56. Clinically, DFFB haploinsufficiency from 1p chr1 loss is associated with oligodendroglioma development, suggesting its role as a tumor suppressor 7. DFFB alterations may serve as biomarkers for systemic lupus erythematosus and other pathological states 12.