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.

• Publication year

  2000

• Venue

  Acta Biochimica Polonica

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18388/ABP.2000_3957PMID 11996094
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mechanisms of induction of apoptotic DNA fragmentation.

  2009cited by this paper
• Structure of the heterodimeric complex between CAD domains of CAD and ICAD

  2000cited by this paper
• Cleavage Preferences of the Apoptotic Endonuclease DFF40 (Caspase-activated DNase or Nuclease) on Naked DNA and Chromatin Substrates*

  2000influential reference
• The biochemistry of apoptosis

  2000cited by this paper
• DFF40/CAD HYPERSENSITIVE SITES ARE POTENTIALLY INVOLVED IN HIGH MOLECULAR WEIGHT DNA FRAGMENTATION DURING APOPTOSIS

  2000cited by this paper
• DNA topoisomerase IIα interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution

  2000influential reference
• Molecular characterization of mitochondrial apoptosis-inducing factor

  1999cited by this paper
• Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis.

  1999cited by this paper
• Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation

  1999cited by this paper
• Activation of the Apoptotic Endonuclease DFF40 (Caspase-activated DNase or Nuclease)

  1999cited by this paper
• Apoptotic nuclear morphological change without DNA fragmentation.

  1999influential reference
• Functional Differences of Two Forms of the Inhibitor of Caspase-activated DNase, ICAD-L, and ICAD-S*

  1999influential reference
• Functional Interaction of DFF35 and DFF45 with Caspase-activated DNA Fragmentation Nuclease DFF40*

  1999cited by this paper
• Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress.

  1999cited by this paper
• Biochemical pathways of caspase activation during apoptosis.

  1999cited by this paper
• Identification of Regulatory and Catalytic Domains in the Apoptosis Nuclease DFF40/CAD*

  1999cited by this paper
• DNA Fragmentation Factor 45-deficient Cells Are More Resistant to Apoptosis and Exhibit Different Dying Morphology than Wild-type Control Cells*

  1999cited by this paper
• A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD

  1998influential reference
• CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor

  1998cited by this paper
• Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45.

  1998cited by this paper
• CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.

  1998cited by this paper
• The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis.

  1998influential reference
• DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis.

  1997influential reference
• Programmed cell death in animal development.

  1997cited by this paper
• Caspases and caspase inhibitors.

  1997cited by this paper
• Apoptosis by death factor.

  1997cited by this paper
• Cellular catabolism in apoptosis: DNA degradation and endonuclease activation

  1996cited by this paper
• Large-scale Fragmentation of Mammalian DNA in the Course of Apoptosis Proceeds via Excision of Chromosomal DNA Loops and Their Oligomers (*)

  1995cited by this paper
• Role of nucleases in apoptosis.

  1994cited by this paper
• Formation of large molecular weight fragments of DNA is a key committed step of apoptosis in thymocytes.

  1994cited by this paper
• Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation.

  1993cited by this paper
• Periodicity of DNA folding in higher order chromatin structures.

  1990cited by this paper
• Apoptosis. The role of the endonuclease.

  1990cited by this paper
• Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation

  1980cited by this paper
• Cell death: the significance of apoptosis.

  1980cited by this paper

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• [Apoptosis, proliferation and spleen histomorphometry of adult female rats with thyroid and ovarian hypofunction].

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