Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins
Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins
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DOI：
10.1038/nature06420
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发表时间：
2008-01-03
期刊：
影响因子：
64.8
通讯作者：
West, Stephen C.
中科院分区：
文献类型：
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作者：
Ahel, Ivan;Ahel, Dragana;West, Stephen C.
蛋白质的翻译后修饰（PTM）在介导蛋白质相互作用和/或特异性蛋白质靶标的募集中起重要作用（1，2）。PTM可以通过添加官能团（例如，乙酰化或磷酸化）、肽（例如，泛素化或类小泛素化）或核苷酸（例如，聚（ADP-核糖基）化）来介导。聚（ADP-核糖基）化通常涉及添加ADP-核糖单元的长链，通过糖苷核糖-核糖键连接（3），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，有丝分裂和凋亡（4）。在这里，我们确定了一个新的聚（ADP-核糖）结合锌指（PBZ）模体在一些真核生物蛋白参与DNA损伤反应和检查点调控。PBZ基序也是翻译后聚（ADP-核糖基）化所必需的.我们证明了在两种代表性的人类蛋白质APLF（aprataxin PNK样因子）和CHFR（具有FHA和RING结构域的检查点蛋白）中聚（ADP-核糖）与该基序的相互作用，并表明CHFR在前期检查点中的作用被PBZ中的突变或聚（ADP-核糖）合成的抑制所废除.
Post- translational modification ( PTM) of proteins plays an important part in mediating protein interactions and/ or the recruitment of specific protein targets(1,2). 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(3), and is critical for a wide range of processes, including DNA repair, regulation of chromosome structure, transcriptional regulation, mitosis and apoptosis(4). 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 posttranslational 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.