Inhibition of DNA polymerase α, DNA polymerase β, terminal deoxynucleotidyl transferase, and DNA ligase II by poly(ADP-ribosyl)ation reaction in vitro
Inhibition of DNA polymerase α, DNA polymerase β, terminal deoxynucleotidyl transferase, and DNA ligase II by poly(ADP-ribosyl)ation reaction in vitro
复制标题
体外聚（ADP-核糖基）化反应对 DNA 聚合酶 α、DNA 聚合酶 β、末端脱氧核苷酸转移酶和 DNA 连接酶 II 的抑制
DOI：
10.1016/0006-291x(85)91644-4
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发表时间：
1985
影响因子：
3.1
通讯作者：
T. Kamiya
中科院分区：
文献类型：
--
作者：
K. Yoshihara;A. Itaya;Yasuharu Tanaka;Y. Ohashi;Kimihiko Ito;H. Teraoka;K. Tsukada;A. Matsukage;T. Kamiya
DNA聚合酶α1、DNA聚合酶β、末端脱氧核苷酸转移酶或DNA连接酶II在重组聚（ADP-核糖基）化酶系统中的孵育显著抑制这些酶的活性。聚（ADP-核糖）合成所需的组件，包括聚（ADP-核糖）聚合酶，NAD+，DNA和Mg 2+都是必不可少的观察到的抑制。然而，纯化的聚（ADP-核糖）本身对所有这些酶都有轻微的抑制作用。此外，DNA聚合酶α、DNA聚合酶β和末端脱氧核苷酸转移酶的抑制活性通过温和的碱处理而大部分恢复（观察到3至4倍的刺激），该方法已知水解聚（ADP-核糖）和受体蛋白之间的碱不稳定酯键。所有这些结果都有力地表明，这四种核酶的抑制是由于酶分子本身或这些酶的某些调节蛋白的聚（ADP-核糖基）化。
Incubation of DNA polymerase α1, DNA polymerase β, terminal deoxynucleotidyl transferase, or DNA ligase II in a reconstituted poly(ADP-ribosyl)ating enzyme system markedly suppressed the activity of these enzymes. Components required for poly(ADP-ribose) synthesis including poly(ADP-ribose) polymerase, NAD+, DNA, and Mg2+were all essential for the observed suppression. Purified poly(ADP-ribose) itself, however, was slightly inhibitory to all of these enzymes. Furtheremore, the suppressed activities of DNA polymerase α, DNA polymerase β, and terminal deoxynucleotidyl transferase were largely restored (3 to 4-fold stimulation was observed) by a mild alkaline treatment, a procedure known to hydrolyze alkaline-labile ester linkage between poly(ADP-ribose) and an acceptor protein. All of these results strongly suggest that the four nuclear enzymes were inhibited as a result of poly(ADP-ribosyl)ation of either the enzyme molecule itself or some regulatory proteins of these enzymes.