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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle*
  • Cell Line
  • DNA Damage
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Poly Adenosine Diphosphate Ribose / biosynthesis
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly-ADP-Ribose Binding Proteins
  • Protein Binding
  • Protein Processing, Post-Translational
  • Ubiquitin-Protein Ligases
  • Ubiquitination
  • Zinc Fingers / physiology*


  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Phosphoproteins
  • Poly-ADP-Ribose Binding Proteins
  • Poly Adenosine Diphosphate Ribose
  • CHFR protein, human
  • Ubiquitin-Protein Ligases
  • APLF protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase