Ahel Ivan, Ahel Dragana, Matsusaka Takahiro, Clark Allison J, Pines Jonathon, Boulton Simon J, West Stephen C
Genetic Recombination and, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Nature. 2008 Jan 3;451(7174):81-5. doi: 10.1038/nature06420.
Post-translational modification (PTM) of proteins plays an important part in mediating protein interactions and/or the recruitment of specific protein targets. PTM can be mediated by the addition of functional groups (for example, acetylation or phosphorylation), peptides (for example, ubiquitylation or sumoylation), or nucleotides (for example, poly(ADP-ribosyl)ation). Poly(ADP-ribosyl)ation often involves the addition of long chains of ADP-ribose units, linked by glycosidic ribose-ribose bonds, and is critical for a wide range of processes, including DNA repair, regulation of chromosome structure, transcriptional regulation, mitosis and apoptosis. Here we identify a novel poly(ADP-ribose)-binding zinc finger (PBZ) motif in a number of eukaryotic proteins involved in the DNA damage response and checkpoint regulation. The PBZ motif is also required for post-translational poly(ADP-ribosyl)ation. We demonstrate interaction of poly(ADP-ribose) with this motif in two representative human proteins, APLF (aprataxin PNK-like factor) and CHFR (checkpoint protein with FHA and RING domains), and show that the actions of CHFR in the antephase checkpoint are abrogated by mutations in PBZ or by inhibition of poly(ADP-ribose) synthesis.
蛋白质的翻译后修饰（PTM）在介导蛋白质相互作用和/或招募特定蛋白质靶点方面发挥着重要作用。PTM可通过添加官能团（例如乙酰化或磷酸化）、肽（例如泛素化或类泛素化）或核苷酸（例如聚（ADP-核糖）化）来介导。聚（ADP-核糖）化通常涉及通过糖苷核糖-核糖键连接的长链ADP-核糖单元的添加，并且对于广泛的过程至关重要，包括DNA修复、染色体结构调节、转录调节、有丝分裂和细胞凋亡。在这里，我们在许多参与DNA损伤反应和检查点调节的真核蛋白质中鉴定出一种新型的聚（ADP-核糖）结合锌指（PBZ）基序。PBZ基序对于翻译后聚（ADP-核糖）化也是必需的。我们在两种代表性的人类蛋白质APLF（共济失调毛细血管扩张症突变蛋白PNK样因子）和CHFR（具有FHA和RING结构域的检查点蛋白）中证明了聚（ADP-核糖）与该基序的相互作用，并表明PBZ中的突变或聚（ADP-核糖）合成的抑制消除了CHFR在前期检查点中的作用。
