title: DNA repair factor APLF is a histone chaperone.
abstract: 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.
authors.affiliation: Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Pawan Vinod
authors.initials: PV
authors.lastname: Mehrotra
authors.forename: Dragana
authors.initials: D
authors.lastname: Ahel
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Ria
authors.initials: R
authors.lastname: Weston
authors.forename: Nicola
authors.initials: N
authors.lastname: Wiechens
authors.forename: Rolf
authors.initials: R
authors.lastname: Kraehenbuehl
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D056890:Eukaryota / Q000235:genetics; D006367:HeLa Cells; D056488:Histone Chaperones / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017385:Sequence Homology; D012359:tRNA Methyltransferases
chemical_list: D056488:Histone Chaperones; D006657:Histones; D010750:Phosphoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C498548:TRMO protein, human; D012359:tRNA Methyltransferases; C520557:APLF protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase