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在缺乏聚(ADP - 核糖)聚合酶的情况下细胞对DNA损伤的反应

Cellular responses to DNA damage in the absence of Poly(ADP-ribose) polymerase.

作者信息

Le Rhun Y, Kirkland J B, Shah G M

机构信息

Laboratory for Skin Research, Hospital Research Center for University Laval, CHUL Research Center of CHUQ, Québec, Québec, G1V 4G2, Canada.

出版信息

Biochem Biophys Res Commun. 1998 Apr 7;245(1):1-10. doi: 10.1006/bbrc.1998.8257.

DOI:10.1006/bbrc.1998.8257
PMID:9535773
Abstract

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.

摘要

聚(ADP - 核糖)聚合酶(PARP)是一种核酶,可被DNA链断裂催化激活。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多肽或其酶促产物的确切作用仍不明确。最近对两种不同的PARP基因敲除小鼠的研究表明,PARP在全身γ射线照射后维持基因组完整性和存活反应中具有有益作用。其他研究表明,PARP在缺血再灌注损伤后神经元细胞死亡中起重要作用。在缺乏两种主要DNA链断裂结合蛋白PARP和DNA依赖性蛋白激酶活性的模型系统中,PARP在DNA链断裂处的重组抑制功能更为明显。本综述总结了两种PARP基因敲除小鼠的异同,并重新分析了PARP在细胞对DNA损伤的各种反应中的作用。

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Cellular responses to DNA damage in the absence of Poly(ADP-ribose) polymerase.在缺乏聚(ADP - 核糖)聚合酶的情况下细胞对DNA损伤的反应
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Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair.聚(ADP - 核糖)聚合酶的抑制会激活ATM,而ATM是后续同源重组修复所必需的。
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PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways.PARP-1和Ku通过不同的非同源末端连接途径竞争修复DNA双链断裂。
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