ROLE OF POLY(ADP-RIBOSE) FORMATION IN DNA-REPAIR
ROLE OF POLY(ADP-RIBOSE) FORMATION IN DNA-REPAIR
复制标题
DOI：
10.1038/356356a0
复制
发表时间：
1992-03-26
期刊：
影响因子：
64.8
通讯作者：
LINDAHL, T
中科院分区：
文献类型：
--
作者：
SATOH, MS;LINDAHL, T
丰富的核酶聚 (ADP-核糖) 聚合酶催化烟酰胺腺嘌呤二核苷酸 (NAD+) 1-5 合成聚 (ADP-核糖)。该蛋白具有一个包含两个锌指的 N 端 DNA 结合结构域，该结构域通过包含多个谷氨酸残基的短区域（这些谷氨酸残基是自聚（ADP-核糖基）化 6-8 的位点）与 C 端 NAD+ 结合结构域连接。细胞内产生聚（ADP-核糖）是由在 DNA 7 中产生链中断的试剂诱导的。支链均聚物链的大小可能达到 200-300 个残基 9，但在合成后会迅速降解。聚（ADP-核糖）合成的功能尚不清楚，尽管它似乎是 DNA 修复所必需的 10,11。在这里，我们描述了一种人类无细胞系统，该系统能够表征聚（ADP-核糖）合成在 DNA 修复中的作用。结果表明，未修饰的聚合酶分子与 DNA 链断裂紧密结合；然后蛋白质的自聚（ADP-核糖基）化影响其释放，并允许 DNA 修复酶进入损伤部位。
THE abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+) 1-5. This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD+-binding domain by a short region containing several glutamic acid residues that are sites of auto-poly(ADP-ribosyl)ation 6-8. The intracellular production of poly(ADP-ribose) is induced by agents that generate strand interruptions in DNA 7. The branched homopolymer chains may attain a size of 200-300 residues 9 but are rapidly degraded after synthesis. The function of poly(ADP-ribose) synthesis is not clear, although it seems to be required for DNA repair 10,11. Here we describe a human cell-free system that enables the role of poly(ADP-ribose) synthesis in DNA repair to be characterized. The results indicate that unmodified polymerase molecules bind tightly to DNA strand breaks; auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes.