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

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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.

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Authors and Affiliations

  1. Department of Experimental and Clinical Radiobiology, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, 44-100, Gliwice, Poland

    Piotr Widlak

  2. Department of Molecular Biology, Southwestern Medical Center, University of Texas, Dallas, Texas, 75390, USA

    William T. Garrard

  3. Department of Radiobiology, Center of Oncology—Maria Sklodowska-Curie Memorial Institute, Branch in Gliwice, Poland

    Piotr Widlak

  4. 15 Wybrzeże AK, Gliwice, 44-100, Poland

    Piotr Widlak

Authors
  1. Piotr Widlak
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  2. William T. Garrard
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Correspondence to Piotr Widlak.

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Widlak, P., Garrard, W.T. The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. Apoptosis 11, 1331–1337 (2006). https://doi.org/10.1007/s10495-006-6983-0

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  • DOI: https://doi.org/10.1007/s10495-006-6983-0

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