Durkacz B W, Omidiji O, Gray D A, Shall S
Nature. 1980 Feb 7;283(5747):593-6. doi: 10.1038/283593a0.
Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP-ribose) polymerase, which uses the coenzyme NAD+ to ADP-ribosylate chromatin proteins. The modification consists largely of mono(ADP-ribose), but long, homopolymer chains of (ADP-ribose) are also present. Various physiological functions have been suggested for (ADP-ribose)n. Here we demonstrate that one function of (ADP-ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP-ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD.
染色质蛋白通过至少五种不同的过程进行共价修饰;在任何情况下,其精确的生理功能都尚未确定。这些合成后共价修饰中的一种是由聚(ADP - 核糖)聚合酶催化的,该酶利用辅酶NAD⁺对染色质蛋白进行ADP - 核糖基化。这种修饰主要由单(ADP - 核糖)组成,但也存在长的(ADP - 核糖)同聚物链。对于(ADP - 核糖)ₙ已经提出了各种生理功能。在这里我们证明(ADP - 核糖)ₙ的一个功能是参与细胞从DNA损伤中的恢复。聚(ADP - 核糖)聚合酶的特异性抑制剂可阻止由硫酸二甲酯引起的DNA链断裂的重新连接,从而增强细胞毒性。通过营养耗尽细胞中的NAD也可阻止链断裂的重新连接。