title: ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response to UV irradiation.
abstract: Successful DNA repair within chromatin requires coordinated interplay of histone modifications, chaperones and remodelers for allowing access of repair and checkpoint machineries to damaged sites. Upon completion of repair, ordered restoration of chromatin structure and key epigenetic marks herald the cell's normal function. Here, we demonstrate such a restoration role of H3K56 acetylation (H3K56Ac) mark in response to ultraviolet (UV) irradiation of human cells. A fast initial deacetylation of H3K56 is followed by full renewal of an acetylated state at ~24-48 h post-irradiation. Histone chaperone, anti-silencing function-1 A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in turn, is needed for the dephosphorylation of γ-H2AX and cellular recovery from checkpoint arrest. On the other hand, completion of DNA damage repair is not dependent on ASF1A or H3K56Ac. H3K56Ac restoration is regulated by ataxia telangiectasia mutated (ATM) checkpoint kinase. These cross-talking molecular cellular events reveal the important pathway components influencing the regulatory function of H3K56Ac in the recovery from UV-induced checkpoint arrest.
authors: Department of Radiology, The Ohio State University, Columbus, OH 43210, USA.
authors: Aruna
authors: A
authors: Battu
authors: Alo
authors: A
authors: Ray
authors: Altaf A
authors: AA
authors: Wani
mesh_terms: D000107:Acetylation; D064007:Ataxia Telangiectasia Mutated Proteins; D059447:Cell Cycle Checkpoints / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D014466:Ultraviolet Rays
chemical_list: C491641:ASF1A protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D018832:Molecular Chaperones; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D008239:Lysine