Base excision repair is efficient in cells lacking poly(ADP-ribose) polymerase 1

被引:112
作者
Vodenicharov, MD
Sallmann, FR
Satoh, MS
Poirier, GG
机构
[1] Univ Laval, Med Res Ctr, CHUQ, Poly ADP Ribose Metab Grp, Ste Foy, PQ G1V 4G2, Canada
[2] Univ Laval, Med Res Ctr, CHUQ, DNA Repair Grp,Hlth & Environm Unit, Ste Foy, PQ G1V 4G2, Canada
[3] Univ Laval, Fac Med, Ste Foy, PQ G1V 4G2, Canada
关键词
D O I
10.1093/nar/28.20.3887
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 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 wildtype 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 gamma -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.
引用
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页码:3887 / 3896
页数:10
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