The DFF40/CAD endonuclease and its role in apoptosis.

نویسنده

  • P Widłak
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/CAD due to HMG-box interactions with DNA.

The DFF40/CAD endonuclease is primarily responsible for internucleosomal DNA cleavage during the terminal stages of apoptosis. It has been previously demonstrated that the major HMG-box-containing chromatin proteins HMGB1 and HMGB2 stimulate naked DNA cleavage by DFF40/CAD. Here we investigate the mechanism of this stimulation and show that HMGB1 neither binds to DFF40/CAD nor enhances its abil...

متن کامل

Caspase-activated DNase/DNA fragmentation factor 40 mediates apoptotic DNA fragmentation in transient cerebral ischemia and in neuronal cultures.

Nuclear changes, including internucleosomal DNA fragmentation, are characteristic features of neuronal apoptosis resulting from transient cerebral ischemia and related brain insults for which the molecular mechanism has not been elucidated. Recent studies suggest that a caspase-3-mediated mechanism may be involved in the process of nuclear degradation in ischemic neurons. In this study, we clon...

متن کامل

Short Communication DFF40/CAD HYPERSENSITIVE SITES ARE POTENTIALLY INVOLVED IN HIGH MOLECULAR WEIGHT DNA FRAGMENTATION DURING APOPTOSIS

Sequential cleavage of genomic DNA into large-scale DNA fragments of 50-300-kb, followed by formation of monoand oligonucleosomal DNA fragments, is a biochemical hallmark of programmed cell death (apoptosis). The endonuclease DFF40/CAD mediates regulated internucleosomal DNA fragmentation and chromatin condensation in cells undergoing apoptosis. DFF40 hypersensitive sites were detected in purif...

متن کامل

Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells.

Curcumin is a natural pigment that has been shown to induce cell death in many cancer cells; however, the death mode depends on the cell type and curcumin concentration. Here we show that, in Jurkat cells, 50 micromol/L curcumin severely lowers cell survival and induces initial stage of chromatin condensation. It also induces caspase-3, which is sufficient to cleave DNA fragmentation factor 45 ...

متن کامل

DNase γ Is the Effector Endonuclease for Internucleosomal DNA Fragmentation in Necrosis

Apoptosis and necrosis, two major forms of cell death, can be distinguished morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to gene...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Acta biochimica Polonica

دوره 47 4  شماره 

صفحات  -

تاریخ انتشار 2000