title: Poly(ADP-ribosyl)ation-dependent Transient Chromatin Decondensation and Histone Displacement following Laser Microirradiation.
abstract: Chromatin undergoes a rapid ATP-dependent, ATM and H2AX-independent decondensation when DNA damage is introduced by laser microirradiation. Although the detailed mechanism of this decondensation remains to be determined, the kinetics of decondensation are similar to the kinetics of poly(ADP-ribosyl)ation. We used laser microirradiation to introduce DNA strand breaks into living cells expressing a photoactivatable GFP-tagged histone H2B. We find that poly(ADP-ribosyl)ation mediated primarily by poly(ADP-ribose) polymerase 1 (PARP1) is responsible for the rapid decondensation of chromatin at sites of DNA damage. This decondensation of chromatin correlates temporally with the displacement of histones, which is sensitive to PARP inhibition and is transient in nature. Contrary to the predictions of the histone shuttle hypothesis, we did not find that histone H1 accumulated on poly(ADP-ribose) (PAR) in vivo. Rather, histone H1, and to a lessor extent, histones H2A and H2B were rapidly depleted from the sites of PAR accumulation. However, histone H1 returns to chromatin and the chromatin recondenses. Thus, the PARP-dependent relaxation of chromatin closely correlates with histone displacement.
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Strickfaden
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada.
authors.forename: Darin
authors.initials: D
authors.lastname: McDonald
authors.affiliation: the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kruhlak
authors.affiliation: the Oncology Axis, Laval University Hospital Research Center, CHUQ, Faculty of Medicine, Laval University, Quebec G1V 4G2, Canada.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Haince
authors.affiliation: the Northern Ontario School of Medicine, Thunder Bay, Ontario P7B 5E1, Canada.
authors.forename: John P H
authors.initials: JPH
authors.lastname: Th'ng
authors.affiliation: the Oncology Axis, Laval University Hospital Research Center, CHUQ, Faculty of Medicine, Laval University, Quebec G1V 4G2, Canada.
authors.forename: Michele
authors.initials: M
authors.lastname: Rouleau
authors.affiliation: the Department of Biochemistry and Microbiology, University of Victoria, Victoria, B.C. V8W 3P6, Canada,; the Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, HKSAR, and.
authors.forename: Toytaka
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada.
authors.forename: Gareth N
authors.initials: GN
authors.lastname: Corry
authors.affiliation: the Department of Biochemistry and Microbiology, University of Victoria, Victoria, B.C. V8W 3P6, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Ausio
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada.
authors.forename: D Alan
authors.initials: DA
authors.lastname: Underhill
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada.
authors.forename: Guy G
authors.initials: GG
authors.lastname: Poirier
authors.affiliation: From the Department of Oncology, Faculty of Dentistry and Medicine, University of Alberta Alberta T6G 1Z2, Canada,. Electronic address: mhendzel@ualberta.ca.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hendzel
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism* / Q000528:radiation effects*; D042002:Chromatin Assembly and Disassembly / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007834:Lasers; D051379:Mice; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases
keywords: DNA damage; DNA damage response; PARG; PARP-1; chromatin; chromatin remodeling; histone H1; histone modification; poly(ADP-ribosyl)ation