Involvement of poly(ADP-ribose) polymerase in base excision repair

被引:306
作者
Dantzer, F [1 ]
Schreiber, V [1 ]
Niedergang, C [1 ]
Trucco, C [1 ]
Flatter, E [1 ]
De la Rubia, G [1 ]
Oliver, J [1 ]
Rolli, V [1 ]
Ménissier-de Murcia, J [1 ]
de Murcia, G [1 ]
机构
[1] Ecole Super Biotechnol Strasbourg, Commissariat Energie Aton, Lab Convent, UPR 9003,CNRS, F-67400 Illkirch Graffenstaden, France
关键词
poly(ADP-ribose) polymerase; base excision repair; DNA binding protein;
D O I
10.1016/S0300-9084(99)80040-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Poly(ADP-ribose) polymerase (PARP) is a zinc-finger DNA binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these lesions, the immediate poly(ADP-ribosylation) of nuclear proteins converts DNA interruptions into intracellular signals that activate DNA repair or cell death programs. To elucidate the biological function of PARP in vivo, the mouse PARP gene was inactivated by homologous recombination to generate mice lacking a functional PARP gene. PARP knockout mice and the derived mouse embryonic fibroblasts (MEFs) were acutely sensitive to monofunctional alkylating agents and gamma-irradiation demonstrating that PARP is involved in recovery from DNA damage that triggers the base excision repair (BER) process. To address the issue of the role of PARP in BER, the ability of PARP-deficient mammalian cell extracts to repair a single abasic site present on a circular duplex plasmid molecule was tested in a standard in vitro repair assay. The results clearly demonstrate, for the first time, the involvement of PARP in the DNA synthesis step of the base excision repair process. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris.
引用
收藏
页码:69 / 75
页数:7
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