The role of poly(ADP-ribosyl)ation in the adaptive response
The role of poly(ADP-ribosyl)ation in the adaptive response
复制标题
DOI：
10.1016/s0027-5107(96)00123-6
复制
发表时间：
1996-11-04
影响因子：
2.3
通讯作者：
Althaus, FR
中科院分区：
文献类型：
--
作者：
Kleczkowska, HE;Althaus, FR
核酶聚（ADP-核糖）聚合酶的抑制剂已证明聚（ADP-核糖基）化系统参与适应性反应的表达。这种酶是染色质反应循环的关键组成部分，涉及响应 DNA 链断裂而动态合成和降解不同大小的 ADP-核糖聚合物。本报告回顾了最近的工作，重点是聚（ADP-核糖基）化系统在低剂量适应中的反应。结果表明，与高剂量治疗后 DNA 断裂介导的刺激相比，人类细胞对微量烷化剂浓度的适应涉及聚（ADP-核糖）聚合酶的不同激活机制。此外，适应诱导支链聚合物的形成，对组蛋白尾部和选定的其他蛋白质具有非常高的结合亲和力。对适应细胞进行高剂量激发处理进一步增强支化聚合物的形成。我们提出，除了感测 DNA 切口外，聚（ADP-核糖）聚合酶可能是保护细胞免受 DNA 损伤下游事件影响的途径的一部分。
An involvement of the poly(ADP-ribosyl)ation system in the expression of the adaptive response has been demonstrated with inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase. This enzyme is a key component of a reaction cycle in chromatin, involving dynamic synthesis and degradation of variably sized ADP-ribose polymers in response to DNA strand breaks. The present report reviews recent work focussing on the response of the poly(ADP-ribosyl)ation system in low dose adaptation. The results suggest that adaptation of human cells to minute concentrations of an alkylating agent involves a different activation mechanism for poly(ADP-ribose) polymerase than DNA break-mediated stimulation after high dose treatment. Moreover, adaptation induces the formation of branched polymers with a very high binding affinity for histone tails and selected other proteins. High dose challenge treatment of adapted cells further enhances formation of branched polymers. We propose that apart from sensing DNA nicks, poly(ADP-ribose) polymerase may be part of pathway protecting cells from downstream events of DNA damage.