The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

Nat Cell Biol. 2014 Aug;16(8):792-803. doi: 10.1038/ncb3007. Epub 2014 Jul 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Nucleolus / metabolism
  • Conserved Sequence
  • DNA Breaks, Double-Stranded
  • DNA Damage / genetics*
  • DNA Damage / physiology*
  • Gene Silencing
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Interaction Domains and Motifs
  • RNA Polymerase I / metabolism
  • RNA, Ribosomal / genetics*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcription, Genetic


  • Cell Cycle Proteins
  • Multiprotein Complexes
  • NBN protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Ribosomal
  • Recombinant Fusion Proteins
  • TCOF1 protein, human
  • Green Fluorescent Proteins
  • RNA Polymerase I