Nonisotopic methods for determination of poly(ADP-ribose) levels and detection of poly(ADP-ribose) polymerase

Curr Protoc Cell Biol. 2004 Feb:Chapter 18:Unit18.7. doi: 10.1002/0471143030.cb1807s21.

Abstract

Poly(ADP-ribosyl)ation is a post-translational modification catalyzed mostly by the 116-kDa enzyme poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme that transfers an ADP-ribose moiety onto a limited number of nuclear proteins, including itself. When cells are exposed to environmental stresses such as alkylating agents or free radicals, there is up to a 500-fold increase in net poly(ADP-ribose) synthesis in response to DNA strand breaks. The enzyme responsible for 80% to 90% of this stimulated poly(ADP-ribose) synthesis is PARP-1, while other PARPs are responsible for the remaining 10% to 20%. The physiological meaning of these phenomena is not clear; however, it can be interpreted as a way of translating an event occurring on DNA to the nucleus by protein modification and finally to the cytoplasm via NAD(+) depletion. It has also been proposed that the presence of negatively charged poly(ADP-ribose) at the site of DNA damage may play several roles in regulation of base excision repair, p53 functions, and apoptosis. This unit describes protocols for measuring the levels of poly(ADP-ribose) in cells using nonisotopic reagents and for identifying the poly(ADP-ribose) polymerase enzymes present in cells.

MeSH terms

  • Animals
  • Cell Death
  • Cells, Cultured
  • Clinical Laboratory Techniques*
  • Electrophoresis
  • Enzyme-Linked Immunosorbent Assay
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • Poly Adenosine Diphosphate Ribose / analysis*
  • Poly(ADP-ribose) Polymerases / analysis*
  • Poly(ADP-ribose) Polymerases / chemistry

Substances

  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases