Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins

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.