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

Piotr Widlak, William T. Garrard

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 1 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

Fingerprint Dive into the research topics of 'The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions'. Together they form a unique fingerprint.

Cite this