DFFB, also known as DNA fragmentation factor subunit beta, is involved in the process of cell-free DNA (cfDNA) fragmentation. cfDNA is a non-invasive biomarker for cancer and prenatal testing. DFFB, along with other nucleases like DNASE1 and DNASE1L3, contributes to the step-by-step fragmentation of cfDNA. Initially, cfDNA is generated intracellularly with the action of DFFB, intracellular DNASE1L3, and other nucleases, and then extracellular fragmentation continues with circulating DNASE1L3 and DNASE1 [1].

In nuclease-deficient mouse models, analysis of cfDNA fragment ends shows that DFFB has a specific cutting preference, revealing its role in the cfDNA fragmentation process [1]. In Dffb-deficient mice, the proportion of long cfDNA molecules originating from transcription start sites is lower compared to wild-type mice, providing insights into the biological properties of long cfDNA molecules [2]. Also, the deletion of Dffb in mouse models shows less significant effects on the jaggedness of different-sized plasma DNA fragments, compared to the deletion of Dnase1l3 [3].

In summary, DFFB plays a crucial role in the intracellular generation step of cfDNA fragmentation. Studies using Dffb-deficient mouse models have provided valuable insights into cfDNA fragmentation and the biological properties of cfDNA, which may have implications for understanding diseases related to cfDNA dysregulation, such as cancer and systemic lupus erythematosus.