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Genome Degradation by DNAS1L3 Endonuclease

A Key PARP-1-Regulated Event in Apoptosis
  • A. Hamid Boulares
  • Alexander G. Yakovlev
  • Mark E. Smulson
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

Degradation of chromatin into internucleosomal fragments, a prevailing hallmark of apoptosis in most cells and tissues, has been tightly associated with a Ca2+ and Mg2+-dependent endonuclease activity. Several candidate enzymes have been identified as important players in this process. Several decades ago, murine and bovine Ca2+ and Mg2+-dependent endonucleases were observed to be inhibited by poly(ADP-ribosyl)ation in a reaction mediated by PARP-1. PARP-1 is one of the earliest nuclear enzymes to be targeted for degradation by caspases during apoptosis. Such cleavage is believed to prevent energy depletion in response to DNA damage generated as a result of an activation of apoptotic endonucleases. We have recently identified, cloned, and characterized DNAS1L3 as the human homolog of the unidentified bovine poly(ADP-ribosyl)ation-regulated endonuclease. In this review, we will describe the efforts of our and other laboratories in the elucidation of a role for this endonuclease during apoptosis. We will discuss its dependence on Ca2+ and Mg2+, its inhibition by poly (ADP-ribosyl)ation, and its requirement for PARP-1 cleavage, and subsequent inactivation of PARP-1, for optimal activity during apoptosis.

Keywords

Osteosarcoma Cell Endonuclease Activity Dependent Endonuclease Culture Mouse Hepatocyte Apoptotic Endonuclease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2006

Authors and Affiliations

  • A. Hamid Boulares
    • 1
  • Alexander G. Yakovlev
    • 2
  • Mark E. Smulson
    • 3
  1. 1.Department of Pharmacology and Experimental TherapeuticsLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Department of NeuroscienceGeorgetown University School of MedicineWashington, D.C.USA
  3. 3.Department of Biochemistry and Molecular BiologyGeorgetwon University School of MedicineWashington, D.C.USA

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