Furlini G, Re M C, La Placa M
Institute of Microbiology, University of Bologna, Medical School, S. Orsola Hospital, Bologna, Italy.
Microbiologica. 1991 Apr;14(2):141-8.
Poly(ADP-ribose)polymerase is a chromatin-bound enzyme which is activated by free DNA ends and is therefore stimulated by a variety of DNA-damaging agents. The enzyme transfers the ADP moiety of NAD to nuclear proteins to create protein-bound ADP-ribose polymers. Under conditions favouring an accelerated poly(ADP-ribose) polymer formation, the enzyme may exhaust cellular NAD pools. At the same time, or shortly thereafter ATP levels drop and cell viability eventually declines. As a series of chemical and physical agents which may play a role in activating latent HIV-1 infection or favouring HIV-1 replication, have a DNA-damaging activity, we investigated the behaviour of poly(ADP-ribose)polymerase activity in various types of HIV-1-infected cells. The results obtained show that HIV-1-infected cells to possess an increased poly(ADP-ribosol)ating activity together with an accentuated fragmentation of cellular DNA which are associated with the time course of HIV-1 replication. These data give circumstantial support to the hypothesis that a NAD-depdendent cellular suicide response to DNA damage, could play a role in the death of HIV-1 infected cells. In this respect, the impared immunocompetence of HIV-1-infected patients could bear some resemblance to immune attribution that sometimes accompanies some inborn errors affecting DNA precursor metabolism and DNA integrity.
聚（ADP-核糖）聚合酶是一种与染色质结合的酶，可被游离的DNA末端激活，因此受到多种DNA损伤剂的刺激。该酶将NAD的ADP部分转移至核蛋白，以形成与蛋白结合的ADP-核糖聚合物。在有利于加速聚（ADP-核糖）聚合物形成的条件下，该酶可能会耗尽细胞内的NAD池。与此同时，或在此后不久，ATP水平下降，细胞活力最终降低。由于一系列可能在激活潜伏的HIV-1感染或促进HIV-1复制中起作用的化学和物理因子具有DNA损伤活性，我们研究了聚（ADP-核糖）聚合酶活性在各类HIV-1感染细胞中的表现。所得结果表明，HIV-1感染细胞具有增强的聚（ADP-核糖基）化活性，同时伴有细胞DNA的加剧断裂，这与HIV-1复制的时间进程相关。这些数据间接支持了以下假说，即对DNA损伤的依赖NAD的细胞自杀反应可能在HIV-1感染细胞的死亡中起作用。在这方面，HIV-1感染患者受损的免疫能力可能与某些影响DNA前体代谢和DNA完整性的先天性缺陷有时伴随的免疫归因有一些相似之处。
