Abstract
DFF40/CAD, the major apoptotic nuclease, is specific for double-stranded DNA. However, RNA and single-stranded DNA, though not substrates for the enzyme, compete with double-stranded DNA and inhibit its cleavage by the nuclease. In addition, other anionic polymers, like poly-glutamic acid and heparin also inhibit DFF40/CAD, the latter one being highly effective at nanomolar concentrations. The inhibitory poly-anions bind to the nuclease and impair its ability to bind double-stranded DNA. We propose that such poly-anions bind to the positively charged surface formed by α4 helices of the DFF40/CAD homodimer. This surface has been proposed recently to bind to either the major groove of DNA or poly (ADP-ribose), another inhibitor of the nuclease.
Original language | English (US) |
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Pages (from-to) | 1331-1337 |
Number of pages | 7 |
Journal | Apoptosis |
Volume | 11 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2006 |
Keywords
- Apoptosis
- CAD
- DFF
- Heparin
- Nuclease
- Poly(ADP-ribose)
- RNA
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Cancer Research