The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions

Piotr Widlak, William T. Garrard

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1331-1337
Number of pages7
JournalApoptosis
Volume11
Issue number8
DOIs
StatePublished - Aug 2006

Fingerprint

Endonucleases
Heparin
Computer aided design
RNA
DNA
Anions
Poly Adenosine Diphosphate Ribose
Single-Stranded DNA
Glutamic Acid
Polymers
polyanions
Substrates
Enzymes

Keywords

  • Apoptosis
  • CAD
  • DFF
  • Heparin
  • Nuclease
  • Poly(ADP-ribose)
  • RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. / Widlak, Piotr; Garrard, William T.

In: Apoptosis, Vol. 11, No. 8, 08.2006, p. 1331-1337.

Research output: Contribution to journalArticle

Widlak, Piotr ; Garrard, William T. / The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. In: Apoptosis. 2006 ; Vol. 11, No. 8. pp. 1331-1337.
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