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, and Dffb, along with DNASE1 and DNASE1L3, plays a role in the step-by-step fragmentation of cfDNA. It first acts intracellularly, contributing to the generation of cfDNA [1].

In Dffb-deficient mice, the proportion of long cfDNA molecules originating from transcription start sites is lower compared to wild-type mice, indicating its role in the fragmentation of long cfDNA molecules [2]. Also, deletion of Dffb in mouse models led to certain aberrations in the profile of plasma DNA jagged ends, although these effects were less significant compared to Dnase1l3 deletion regarding different sizes of DNA fragments [3].

In conclusion, Dffb is essential for the intracellular stage of cfDNA fragmentation. Studies using Dffb-deficient mouse models have provided insights into its role in cfDNA fragmentation, especially in relation to the fragmentation of long cfDNA molecules and the formation of plasma DNA jagged ends, which may have implications for understanding diseases where cfDNA is a biomarker.

References:

1. Han, Diana S C, Ni, Meng, Chan, Rebecca W Y, Chiu, Rossa W K, Lo, Y M Dennis. 2020. The Biology of Cell-free DNA Fragmentation and the Roles of DNASE1, DNASE1L3, and DFFB. In American journal of human genetics, 106, 202-214. doi:10.1016/j.ajhg.2020.01.008. https://pubmed.ncbi.nlm.nih.gov/32004449/

2. Che, Huiwen, Jiang, Peiyong, Choy, L Y Lois, Chan, K C Allen, Lo, Y M Dennis. 2024. Genomic origin, fragmentomics, and transcriptional properties of long cell-free DNA molecules in human plasma. In Genome research, 34, 189-200. doi:10.1101/gr.278556.123. https://pubmed.ncbi.nlm.nih.gov/38408788/

3. Ding, Spencer C, Chan, Rebecca W Y, Peng, Wenlei, Allen Chan, K C, Dennis Lo, Y M. . Jagged Ends on Multinucleosomal Cell-Free DNA Serve as a Biomarker for Nuclease Activity and Systemic Lupus Erythematosus. In Clinical chemistry, 68, 917-926. doi:10.1093/clinchem/hvac050. https://pubmed.ncbi.nlm.nih.gov/35587043/