title: Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage.
abstract: Chromatin remodeling is tightly linked to all DNA-transacting activities. To study chromatin remodeling during DNA repair, we established quantitative fluorescence imaging methods to measure the exchange of histones in chromatin in living cells. We show that particularly H2A and H2B are evicted and replaced at an accelerated pace at sites of UV-induced DNA damage. This accelerated exchange of H2A/H2B is facilitated by SPT16, one of the two subunits of the histone chaperone FACT (facilitates chromatin transcription) but largely independent of its partner SSRP1. Interestingly, SPT16 is targeted to sites of UV light-induced DNA damage-arrested transcription and is required for efficient restart of RNA synthesis upon damage removal. Together, our data uncover an important role for chromatin dynamics at the crossroads of transcription and the UV-induced DNA damage response.
authors: Department of Genetics, Erasmus Medical Centre, Rotterdam 3015 GE, The Netherlands.
authors: Christoffel
authors: C
authors: Dinant
authors: Giannis
authors: G
authors: Ampatziadis-Michailidis
authors: Hannes
authors: H
authors: Lans
authors: Maria
authors: M
authors: Tresini
authors: Anna
authors: A
authors: Lagarou
authors: Malgorzata
authors: M
authors: Grosbart
authors: Arjan F
authors: AF
authors: Theil
authors: Wiggert A
authors: WA
authors: van Cappellen
authors: Hiroshi
authors: H
authors: Kimura
authors: Jiri
authors: J
authors: Bartek
authors: Maria
authors: M
authors: Fousteri
authors: Adriaan B
authors: AB
authors: Houtsmuller
authors: Wim
authors: W
authors: Vermeulen
authors: Jurgen A
authors: JA
authors: Marteijn
mesh_terms: D015153:Blotting, Western; D018797:Cell Cycle Proteins; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D009707:Nucleosomes; C073537:SSRP1 protein, human; C489489:SUPT16H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D012313:RNA