Cellular responses to DNA damage in the absence of Poly(ADP-ribose) polymerase.
Cellular responses to DNA damage in the absence of Poly(ADP-ribose) polymerase.
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DOI：
10.1006/bbrc.1998.8257
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发表时间：
1998-04
影响因子：
3.1
通讯作者：
Y. L. Rhun;J. Kirkland;G. Shah
中科院分区：
文献类型：
--
作者：
Y. L. Rhun;J. Kirkland;G. Shah
聚(ADP-核糖)聚合酶(PARP)是一种核酶，可被DNA链中断催化激活。PARP参与了细胞对遗传毒性损伤的不同反应，包括细胞存活、DNA修复、转化和细胞死亡。然而，PARP多肽或其酶产物的确切作用仍不清楚。最近对两种不同的PARP基因敲除小鼠的研究表明，PARP在维持基因组完整性和全身伽玛射线照射后的生存反应方面具有有益的作用。其他研究也证实了PARP在脑缺血再灌注损伤后神经细胞死亡中的作用。在两种主要的DNA链断裂结合蛋白PARP和DNA依赖的蛋白激酶活性缺乏的模型系统中，PARP在DNA链断裂时的重组抑制作用更加明显。本文总结了两种PARP基因敲除小鼠的异同，并重新分析了PARP在不同细胞对DNA损伤反应中的作用。
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which is catalytically activated by DNA strand interruptions. The involvement of PARP has been implicated in different cellular responses to genotoxic damage, including cell survival, DNA repair, transformation, and cell death. However, the exact contribution of PARP polypeptide or its enzymatic product has remained ill defined. Recent studies with two different PARP knock out mice have demonstrated the beneficial role of PARP in maintaining genomic integrity and in survival responses after exposure to whole body gamma-irradiation. Other studies have demonstrated the instrumental role of PARP in death of the neuronal cells after ischemia-reperfusion injury. The recombination inhibiting function of PARP at DNA strand breaks was more evident in a model system deficient in activities of two major DNA strand break binding proteins, PARP and DNA-dependent protein kinase. The present review summarizes similarities and differences obtained with the two PARP knock out mice and reanalyzes the role of PARP in various cellular responses to DNA damage.