A Dual Approach in the Study of Poly (ADP-ribose) Polymerase: In Vitro Random Mutagenesis and Generation of Deficient Mice

Mol Cell Biochem. 1999 Mar;193(1-2):53-60.

Abstract

A dual approach to the study of poly (ADP-ribose)polymerase (PARP) in terms of its structure and function has been developed in our laboratory. Random mutagenesis of the DNA binding domain and catalytic domain of the human PARP, has allowed us to identify residues that are crucial for its enzymatic activity. In parallel PARP knock-out mice were generated by inactivation of both alleles by gene targeting. We showed that: (i) they are exquisitely sensitive to gamma-irradiation, (ii) they died rapidly from acute radiation toxicity to the small intestine, (iii) they displayed a high genomic instability to gamma-irradiation and MNU injection and, (iv) bone marrow cells rapidly underwent apoptosis following MNU treatment, demonstrating that PARP is a survival factor playing an essential and positive role during DNA damage recovery and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Apoptosis
  • Body Weight
  • Catalysis
  • Escherichia coli / genetics
  • Humans
  • Mice
  • Mice, Knockout*
  • Models, Genetic
  • Models, Molecular
  • Mutagenesis*
  • Poly(ADP-ribose) Polymerases / genetics*
  • Sister Chromatid Exchange

Substances

  • Poly(ADP-ribose) Polymerases