title: The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.
abstract: Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.
authors: 1] Department of Gynecology, University Hospital and University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland [2] The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Dorthe H
authors: DH
authors: Larsen
authors: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Flurina
authors: F
authors: Hari
authors: MRC National Institute of Medical Research, Division of Protein Structure, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: Julie A
authors: JA
authors: Clapperton
authors: Department of Gynecology, University Hospital and University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland.
authors: Myriam
authors: M
authors: Gwerder
authors: Department of Gynecology, University Hospital and University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland.
authors: Katrin
authors: K
authors: Gutsche
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Matthias
authors: M
authors: Altmeyer
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Stephanie
authors: S
authors: Jungmichel
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Luis I
authors: LI
authors: Toledo
authors: Department of Gynecology, University Hospital and University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland.
authors: Daniel
authors: D
authors: Fink
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Maj-Britt
authors: MB
authors: Rask
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Merete
authors: M
authors: Grøfte
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Claudia
authors: C
authors: Lukas
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Michael L
authors: ML
authors: Nielsen
authors: MRC National Institute of Medical Research, Division of Protein Structure, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: Stephen J
authors: SJ
authors: Smerdon
authors: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B DK-2200, Copenhagen, Denmark.
authors: Jiri
authors: J
authors: Lukas
authors: 1] Department of Gynecology, University Hospital and University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland [2] Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Manuel
authors: M
authors: Stucki
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D017124:Conserved Sequence; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics* / Q000502:physiology*; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; C112156:NBN protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012335:RNA, Ribosomal; D011993:Recombinant Fusion Proteins; C105442:TCOF1 protein, human; D049452:Green Fluorescent Proteins; D012318:RNA Polymerase I