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聚(二磷酸腺苷核糖)在人成纤维细胞脱氧核糖核酸修复中的作用

Role of poly(adenosine diphosphate ribose) in deoxyribonucleic acid repair in human fibroblasts.

作者信息

James M R, Lehmann A R

出版信息

Biochemistry. 1982 Aug 17;21(17):4007-13. doi: 10.1021/bi00260a016.

Abstract

We have investigated the role of poly(adenosine diphosphate ribose) in DNA repair in human fibroblasts by observing the effects of 3-aminobenzamide (3AB), a specific inhibitor of poly(ADP-ribose) synthesis, on various aspects of DNA repair. After treatment of human fibroblasts with dimethyl sulfate (DMS), 3AB retarded the joining of strand breaks; unscheduled DNA synthesis was unaffected after low doses of DMS but was stimulated after high doses. 3AB also enhanced the cytotoxicity of DMS. After gamma irradiation there was a slight inhibition by 3AB of the rejoining of single-strand breaks but no effect on the rejoining of double-strand breaks, unscheduled DNA synthesis, DNA replicative synthesis, or cytotoxicity. There were no effects of 3AB on the repair of UV damage. On the basis of the different kinetics of the various steps of excision repair processes after different treatments of fibroblasts, our results are interpreted as evidence that the synthesis of poly(ADP-ribose) is involved in the ligation step of excision repair.

摘要

我们通过观察聚(ADP - 核糖)合成的特异性抑制剂3 - 氨基苯甲酰胺(3AB)对DNA修复各个方面的影响,研究了聚(腺苷二磷酸核糖)在人成纤维细胞DNA修复中的作用。用人成纤维细胞经硫酸二甲酯(DMS)处理后,3AB延缓了链断裂的连接;低剂量DMS处理后,DNA非预定合成不受影响,但高剂量处理后会受到刺激。3AB还增强了DMS的细胞毒性。γ射线照射后,3AB对单链断裂的重新连接有轻微抑制作用,但对双链断裂的重新连接、DNA非预定合成、DNA复制合成或细胞毒性没有影响。3AB对紫外线损伤的修复没有作用。根据成纤维细胞不同处理后切除修复过程各个步骤的不同动力学,我们的结果被解释为聚(ADP - 核糖)的合成参与切除修复连接步骤的证据。

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