Roles of the major apoptotic nuclease-DNA fragmentation factor-in biology and disease

P. Widlak, W. T. Garrard

Research output: Contribution to journalReview article

58 Scopus citations

Abstract

It has now been more than ten years since the discovery of the major apoptotic nuclease, DNA fragmentation factor (DFF), also known as caspaseactivated DNase (CAD). Here we review the recent literature that has uncovered new insight into DFF's regulation, and both its positive and negative roles in human disease. Cells from mice deficient in DFF still undergo apoptotic death without significant cellautonomous DNA degradation. Their corpses' genomes are subsequently degraded by lysosomal DNase II after phagocytosis. However,DFF-deficient mice are more susceptible to cancer. Indeed, several different cancers in humans are associated with defects in DFF expression and it has been proposed that DFF is a p53-independent tumor suppressor. Negative aspects of DFF expression include contributing to susceptibility to acquire systemic lupus erythematosus, to chromosomal translocations that result in mixed lineage leukemias, and in the possible spreading of oncogenes and HIV due to horizontal gene transfer.

Original languageEnglish (US)
Pages (from-to)263-274
Number of pages12
JournalCellular and Molecular Life Sciences
Volume66
Issue number2
DOIs
StatePublished - Jan 1 2009

Keywords

  • Apoptotic nuclease
  • Autoimmunity
  • CAD
  • Chromatin
  • Chromosome translocations
  • DNA degradation
  • MLL
  • Tumor suppression

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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