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Irreversible binding of poly(ADP)ribose polymerase cleavage product to DNA ends revealed by atomic force microscopy: possible role in apoptosis.

Authors
  • Smulson, M E
  • Pang, D
  • Jung, M
  • Dimtchev, A
  • Chasovskikh, S
  • Spoonde, A
  • Simbulan-Rosenthal, C
  • Rosenthal, D
  • Yakovlev, A
  • Dritschilo, A
Type
Published Article
Journal
Cancer research
Publication Date
Aug 15, 1998
Volume
58
Issue
16
Pages
3495–3498
Identifiers
PMID: 9721847
Source
Medline
License
Unknown

Abstract

During apoptosis, DNA undergoes fragmentation and caspase-3 cleaves poly(ADP-ribose) polymerase (PARP) into both a 24-kDa fragment containing the DNA binding domain and an 89-kDa fragment containing the catalytic and automodification domains. Atomic force microscopy revealed that recombinant full-length PARP bound to plasmid DNA fragments and linked them into chainlike structures. Automodification of PARP in the presence of NAD+ resulted in its dissociation from the DNA fragments, which, nevertheless, remained physically aligned. A recombinant 28-kDa fragment of PARP containing the DNA binding domain but lacking the automodification domain irreversibly bound to and linked DNA fragments in the absence or presence of NAD+. Identical results were obtained on incubation of internucleosomal DNA fragments from apoptotic cells with the products of cleavage of recombinant PARP by purified caspase-3. The 24-kDa product of PARP cleavage by caspase-3 may contribute to the irreversibility of apoptosis by blocking the access of DNA repair enzymes to DNA strand breaks.

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