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PMID: 10331638 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular and cellular biochemistry ·Vol. 193 ·No. 1-2 ·1999-03-00 ·Pages 53-60

Trucco C, Rolli V, Oliver FJ, Flatter E, Masson M, Dantzer F, Niedergang C, Dutrillaux B, Ménissier-de Murcia J, de Murcia G

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.

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
Chemicals
Poly(ADP-ribose) Polymerases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Trucco C
Ecole Supérieure de Biotechnologie de Strasbourg, UPR 9003 du Centre National de la Recherche Scientifique Cancérogénèse et Mutagénèse Moléculaire et Structurale, Illkirch-Graffenstaden, France.
Rolli V
Oliver F J
Flatter E
Masson M
Dantzer F
Niedergang C
Dutrillaux B
Ménissier-de Murcia J
de Murcia G
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Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
Published
1999-03-00
Pages
53-60
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
External Links
PubMed source View journal details
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