Eki T
Division of Human Genome Research and Gene Bank, Tsukuba Life Science Center, Ibaraki, Japan.
FEBS Lett. 1994 Dec 19;356(2-3):261-6. doi: 10.1016/0014-5793(94)01280-6.
The influence of poly (ADP-ribose) polymerase (PARP) and poly ADP-ribosylation on DNA synthesis supported by human replicative DNA polymerase (DNA pol) alpha, delta, and epsilon has been examined using the replication system containing poly(dA)4500-oligo(dT)12-18 as the template primer. PARP alone inhibited the pol activities in a dose-dependent manner even in the presence of the accessory factors for DNA pol delta, proliferating cell nuclear antigen (PCNA) and activator 1 (Al; RF-C). Both DNA pol alpha and epsilon activities were decreased approximately 10-fold under the poly ADP-ribosylating condition. In contrast, DNA synthesis by DNA pol delta holoenzyme was not affected by poly ADP-ribosylation like prokaryotic DNA pol's. The analysis of poly(dT) formed by DNA pol alpha and epsilon indicated that poly ADP-ribosylation mainly reduced the frequency of replication. These observations suggest a possibility that PARP acts as a negative regulator for the initiation of DNA replication upon cellular DNA damage.
利用以聚（dA）4500 - 寡聚（dT）12 - 18为模板引物的复制系统，研究了聚（ADP - 核糖）聚合酶（PARP）和聚ADP - 核糖基化对人复制性DNA聚合酶（DNA pol）α、δ和ε所支持的DNA合成的影响。即使在存在DNA pol δ的辅助因子增殖细胞核抗原（PCNA）和激活因子1（Al；RF - C）的情况下，单独的PARP也以剂量依赖的方式抑制聚合酶活性。在聚ADP - 核糖基化条件下，DNA pol α和ε的活性均降低了约10倍。相比之下，DNA pol δ全酶的DNA合成不受聚ADP - 核糖基化的影响，这与原核DNA聚合酶类似。对DNA pol α和ε形成的聚（dT）的分析表明，聚ADP - 核糖基化主要降低了复制频率。这些观察结果提示，PARP有可能在细胞DNA损伤时作为DNA复制起始的负调节因子发挥作用。
