A dual approach in the study of poly (ADP-ribose) polymerase: In vitro random mutagenesis and generation of deficient mice

  • Carlotta Trucco
  • Véronique Rolli
  • F. Javier Oliver
  • Eric Flatter
  • Murielle Masson
  • Françoise Dantzer
  • Claude Niedergang
  • Bernard Dutrillaux
  • Josiane Ménissier-de Murcia
  • Gilbert de Murcia
Part of the Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease book series (DMCB, volume 30)

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 γ-irradiation, (ii) they died rapidly from acute radiation toxicity to the small intestine, (iii) they displayed a high genomic instability to γ-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.

Key words

DNA binding protein NAD metabolism cellular response to DNA damage γ-rays alkylating agents genomic instability apoptosis 

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Carlotta Trucco
    • 1
  • Véronique Rolli
    • 1
  • F. Javier Oliver
    • 1
  • Eric Flatter
    • 1
  • Murielle Masson
    • 1
  • Françoise Dantzer
    • 1
  • Claude Niedergang
    • 1
  • Bernard Dutrillaux
    • 2
  • Josiane Ménissier-de Murcia
    • 1
  • Gilbert de Murcia
    • 1
    • 3
  1. 1.Ecole Supérieure de Biotechnologie de Strasbourg, UPR 9003 du Centre National de la Recherche Scientifique “Cancérogénèse et Mutagénèse Moléculaire et Structurale”Illkirch-GraffenstadenFrance
  2. 2.Département de RadiobiologieCENFARFontenay-aux-RosesFrance
  3. 3.Ecole Supérieure de Biotechnologie de Strasbourg, UPR 9003 du Centre National de la Recherche Scientifique “Cancérogénèse et Mutagénèse Moléculaire et Structurale”Illkirch-GraffenstadenFrance

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