Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Mol Aspects Med. 2013 Dec;34(6):1124-37. doi: 10.1016/j.mam.2013.04.001. Epub 2013 Apr 25.
It is becoming increasingly clear that the nuclear protein, poly-ADP-ribose polymerase 1 (PARP1), plays essential roles in the cell, including DNA repair, translation, transcription, telomere maintenance, and chromatin remodeling. Despite the exciting progress made in understanding the ubiquitous role of poly-ADP-ribose metabolism, a basic mechanism of PARP's activity regulating multiple nuclear processes is yet to be outlined. This review offers a holistic perspective on activity of PARP1, based on empirically observable phenomena. Primary attention is given to mechanisms by which PARP1 regulates a broad range of essential nuclear events, including two complementary processes (1) regulation of protein-nucleic acid interactions by means of protein shuttling and (2) utilizing poly-ADP-ribose as an anionic matrix for trapping, recruiting, and scaffolding proteins.
越来越明显的是,核蛋白聚 ADP-核糖聚合酶 1(PARP1)在细胞中发挥着重要作用,包括 DNA 修复、翻译、转录、端粒维持和染色质重塑。尽管在理解聚 ADP-核糖代谢的普遍作用方面取得了令人兴奋的进展,但 PARP 活性调节多种核过程的基本机制尚未概述。本综述基于经验观察到的现象,提供了对 PARP1 活性的整体观点。主要关注 PARP1 调节广泛的核事件的机制,包括两种互补的过程:(1)通过蛋白质穿梭调节蛋白质-核酸相互作用,(2)利用聚 ADP-核糖作为阴离子基质来捕获、招募和支架蛋白。