Fouquerel Elise, Sobol Robert W
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213, USA.
DNA Repair (Amst). 2014 Nov;23:27-32. doi: 10.1016/j.dnarep.2014.09.004. Epub 2014 Oct 3.
Nicotinamide adenine dinucleotide, NAD(+), is a small metabolite coenzyme that is essential for the progress of crucial cellular pathways including glycolysis, the tricarboxylic acid cycle (TCA) and mitochondrial respiration. These processes consume and produce both oxidative and reduced forms of NAD (NAD(+) and NADH). NAD(+) is also important for ADP(ribosyl)ation reactions mediated by the ADP-ribosyltransferase enzymes (ARTDs) or deacetylation reactions catalyzed by the sirtuins (SIRTs) which use NAD(+) as a substrate. In this review, we highlight the significance of NAD(+) catabolism in DNA repair and cell death through its utilization by ARTDs and SIRTs. We summarize the current findings on the involvement of ARTD1 activity in DNA repair and most specifically its involvement in the trigger of cell death mediated by ARTD1 activation and energy depletion. By sharing the same substrate, the activities of ARTDs and SIRTs are tightly linked, are dependent on each other and are thereby involved in the same cellular processes that play an important role in cancer biology, inflammatory diseases and ischaemia/reperfusion.
烟酰胺腺嘌呤二核苷酸（NAD(+)）是一种小分子代谢辅酶，对于包括糖酵解、三羧酸循环（TCA）和线粒体呼吸在内的关键细胞途径的进行至关重要。这些过程消耗并产生氧化型和还原型的NAD（NAD(+)和NADH）。NAD(+)对于由ADP-核糖基转移酶（ARTDs）介导的ADP（核糖基）化反应或由沉默调节蛋白（SIRTs）催化的脱乙酰化反应也很重要，这些反应将NAD(+)用作底物。在本综述中，我们强调了NAD(+)分解代谢在DNA修复和细胞死亡中的重要性，这是通过ARTDs和SIRTs对其的利用实现的。我们总结了目前关于ARTD1活性参与DNA修复的研究结果，特别是其在由ARTD1激活和能量耗竭介导的细胞死亡触发中的作用。通过共享相同的底物，ARTDs和SIRTs的活性紧密相连、相互依赖，因此参与了在癌症生物学、炎症性疾病和缺血/再灌注中起重要作用的相同细胞过程。
