The Nexus of cfDNA and Nuclease Biology

Trends Genet. 2021 Aug;37(8):758-770. doi: 10.1016/j.tig.2021.04.005. Epub 2021 May 15.


Cell-free DNA (cfDNA) is a widely used noninvasive biomarker for diagnosis and prognosis of multiple disease states. Emerging evidence suggests that cfDNA might not just be passive waste products of cell death but could have a physiological and pathological function in inflammation and autoimmunity. The balance of cfDNA generation and clearance may thus be vital in health and disease. In particular, plasma nuclease activity has been linked to multiple pathologies including cancer and systemic lupus erythematosus (SLE) and associated with profound changes in the nonrandom fragmentation of cfDNA. Lastly, in this review, we explore the effects of DNA fragmentation factor B (DFFB), DNASE1L3, and DNASE1 on cfDNA levels and their fragmentomic profiles, and what these recent insights reveal about the biology of cfDNA.

Keywords: DFFB; DNASE1; DNASE1L3; cell-free DNA; liquid biopsy; nuclease.

Publication types

  • Review

MeSH terms

  • Autoimmunity / genetics
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics*
  • DNA Fragmentation
  • Deoxyribonuclease I / blood
  • Deoxyribonuclease I / genetics*
  • Deoxyribonucleases / blood
  • Deoxyribonucleases / genetics*
  • Endodeoxyribonucleases / blood
  • Endodeoxyribonucleases / genetics*
  • Humans
  • Inflammation / blood
  • Inflammation / genetics
  • Inflammation / pathology
  • Poly-ADP-Ribose Binding Proteins / blood
  • Poly-ADP-Ribose Binding Proteins / genetics*


  • Cell-Free Nucleic Acids
  • Poly-ADP-Ribose Binding Proteins
  • DFFB protein, human
  • DNASE1L3 protein, human
  • Deoxyribonucleases
  • Endodeoxyribonucleases
  • DNASE1 protein, human
  • Deoxyribonuclease I