Beneke Sascha
Institute of Veterinary Pharmacology and Toxicology, University of Zurich Zurich, Switzerland.
Front Genet. 2012 Sep 3;3:169. doi: 10.3389/fgene.2012.00169. eCollection 2012.
The interaction of DNA with proteins in the context of chromatin has to be tightly regulated to achieve so different tasks as packaging, transcription, replication and repair. The very rapid and transient post-translational modification of proteins by poly(ADP-ribose) has been shown to take part in all four. Originally identified as immediate cellular answer to a variety of genotoxic stresses, already early data indicated the ability of this highly charged nucleic acid-like polymer to modulate nucleosome structure, the basic unit of chromatin. At the same time the enzyme responsible for synthesizing poly(ADP-ribose), the zinc-finger protein poly(ADP-ribose) polymerase-1 (PARP1), was shown to control transcription initiation as basic factor TFIIC within the RNA-polymerase II machinery. Later research focused more on PARP-mediated regulation of DNA repair and cell death, but in the last few years, transcription as well as chromatin modulation has re-appeared on the scene. This review will discuss the impact of PARP1 on transcription and transcription factors, its implication in chromatin remodeling for DNA repair and probably also replication, and its role in controlling epigenetic events such as DNA methylation and the functionality of the insulator protein CCCTC-binding factor.
在染色质环境中,DNA与蛋白质的相互作用必须受到严格调控,以实现诸如包装、转录、复制和修复等不同任务。聚(ADP-核糖)对蛋白质进行的非常快速且短暂的翻译后修饰已被证明参与了所有这四个过程。聚(ADP-核糖)最初被确定为细胞对各种基因毒性应激的即时反应,早期数据就已表明这种高度带电的类核酸聚合物能够调节染色质的基本单位——核小体的结构。与此同时,负责合成聚(ADP-核糖)的酶,即锌指蛋白聚(ADP-核糖)聚合酶-1(PARP1),被证明作为RNA聚合酶II机制中的基本因子TFIIC控制转录起始。后来的研究更多地集中在PARP介导的DNA修复和细胞死亡调控上,但在过去几年中,转录以及染色质调节再次成为研究热点。本综述将讨论PARP1对转录和转录因子的影响,其在DNA修复以及可能还有复制的染色质重塑中的作用,以及其在控制表观遗传事件(如DNA甲基化和绝缘子蛋白CCCTC结合因子的功能)中的作用。