Nucleic Acids Research, 2000, Vol. 28, No. 20 3887-3896
© 2000 Oxford University Press
Base excision repair is efficient in cells lacking poly(ADP-ribose) polymerase 1
Poly(ADP-ribose) Metabolism Group and 1DNA Repair Group, Health and Environment Unit, Laval University Medical Research Center, CHUQ and Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Ste-Foy, Quebec G1V 4G2, Canada
Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that is activated by binding to DNA breaks induced by ionizing radiation or through repair of altered bases in DNA by base excision repair. Mice lacking PARP-1 and, in certain cases, the cells derived from these mice exhibit hypersensitivity to ionizing radiation and alkylating agents. In this study we investigated base excision repair in cells lacking PARP-1 in order to elucidate whether their augmented sensitivity to DNA damaging agents is due to an impairment of the base excision repair pathway. Extracts prepared from wild-type cells or cells lacking PARP-1 were similar in their ability to repair plasmid DNA damaged by either X-rays (single-strand DNA breaks) or by N-methyl-N'-nitro-N-nitrosoguanidine (methylated bases). In addition, we demonstrated in vivo that PARP-1-deficient cells treated with N-methyl-N'-nitro-N-nitrosoguanidine repaired their genomic DNA as efficiently as wild-type cells. Therefore, we conclude that cells lacking PARP-1 have a normal capacity to repair single-strand DNA breaks inflicted by X-irradiation or breaks formed during the repair of modified bases. We propose that the hypersensitivity of PARP-1 null mutant cells to 
-irradiation and alkylating agents is not directly due to a defect in DNA repair itself, but rather results from greatly reduced poly(ADP-ribose) formation during base excision repair in these cells.
* To whom correspondence should be addressed. Tel: +1 418 654 2267; Fax: +1 418 654 2159; Email: guy.poirier@crchul.ulaval.ca Present address: Frédéric R. Sallmann, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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