The DFF40/CAD endonuclease and its role in apoptosis.
The sequential generation of large-scale DNA fragments followed by internucleosomal chromatin fragmentation is a biochemical hallmark of apoptosis. One of the nucleases primarily responsible for genomic DNA fragmentation during apoptosis is called DNA Fragmentation Factor 40 (DFF40) or Caspase-activated DNase (CAD). DFF40/CAD is a magnesium-dependent endonuclease specific for double stranded DNA that generates double strand breaks with 3'-hydroxyl ends. DFF40/CAD is activated by caspase-3 that cuts the nuclease's inhibitor DFF45/ICAD. The nuclease preferentially attacks chromatin in the internucleosomal linker DNA. However, the nuclease hypersensitive sites can be detected and DFF40/CAD is potentially involved in large-scale DNA fragmentation as well. DFF40/CAD-mediated DNA fragmentation triggers chromatin condensation that is another hallmark of apoptosis.
Widłak
P
P
Department of Experimental and Clinical Radiobiology, Center of Oncology, Gliwice, Poland. widlak@onkol.instonko.gliwice.pl
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000378:metabolism* / Q000502:physiology*; D019281:Dimerization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D013329:Structure-Activity Relationship
D051017:Apoptosis Regulatory Proteins; D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C109664:caspase-activated DNase inhibitor; C113696:DFFB protein, human; D003851:Deoxyribonucleases