title: The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1.
abstract: The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage.
authors.affiliation: Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin 300192, People's Republic of China. 2008xucchang@gmail.com
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Ozge
authors.initials: O
authors.lastname: Gursoy-Yuzugullu
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Price
mesh_terms: D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2; D002843:Chromatin / Q000528:radiation effects; D042002:Chromatin Assembly and Disassembly / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D010957:Plasmids; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D002843:Chromatin; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009707:Nucleosomes; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C120756:macroH2A histone; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases