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Poly(ADP-ribosyl)ation plays a major role in DNA repair, where it regulates chromatin relaxation as one of the critical events in the repair process. However, the molecular mechanism by which poly(ADP-ribose) modulates chromatin remains poorly understood. Here we identify the poly(ADP-ribose)-regulated protein APLF as a DNA-damage-specific histone chaperone. APLF preferentially binds to the histone H3/H4 tetramer via its C-terminal acidic motif, which is homologous to the motif conserved in the histone chaperones of the NAP1L family (NAP1L motif). We further demonstrate that APLF exhibits histone chaperone activities in a manner that is dependent on its acidic domain and that the NAP1L motif is critical for the repair capacity of APLF in vivo. Finally, we identify structural analogs of APLF in lower eukaryotes with the ability to bind histones and localize to the sites of DNA-damage-induced poly(ADP-ribosyl)ation. Collectively, these findings define the involvement of histone chaperones in poly(ADP-ribose)-regulated DNA repair reactions.

Original publication

DOI

10.1016/j.molcel.2010.12.008

Type

Journal article

Journal

Mol Cell

Publication Date

07/01/2011

Volume

41

Pages

46 - 55

Keywords

Amino Acid Motifs, Animals, Caenorhabditis elegans, Cell Line, DNA Damage, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase, Eukaryota, HeLa Cells, Histone Chaperones, Histones, Humans, Molecular Sequence Data, Phosphoproteins, Protein Interaction Mapping, Proteins, Sequence Homology