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Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation.
- Source :
-
Nature communications [Nat Commun] 2020 Jan 08; Vol. 11 (1), pp. 123. Date of Electronic Publication: 2020 Jan 08. - Publication Year :
- 2020
-
Abstract
- Induction of DNA double-strand breaks (DSBs) in ribosomal DNA (rDNA) repeats is associated with ATM-dependent repression of ribosomal RNA synthesis and large-scale reorganization of nucleolar architecture, but the signaling events that regulate these responses are largely elusive. Here we show that the nucleolar response to rDNA breaks is dependent on both ATM and ATR activity. We further demonstrate that ATM- and NBS1-dependent recruitment of TOPBP1 in the nucleoli is required for inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks. Mechanistically, TOPBP1 recruitment is mediated by phosphorylation-dependent interactions between three of its BRCT domains and conserved phosphorylated Ser/Thr residues at the C-terminus of the nucleolar phosphoprotein Treacle. Our data thus reveal an important cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.
- Subjects :
- Amino Acid Motifs
Ataxia Telangiectasia Mutated Proteins genetics
Carrier Proteins genetics
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cell Nucleolus metabolism
DNA Breaks, Double-Stranded
DNA, Ribosomal metabolism
DNA-Binding Proteins genetics
Humans
Nuclear Proteins chemistry
Nuclear Proteins genetics
Phosphoproteins chemistry
Phosphoproteins genetics
Protein Binding
RNA, Ribosomal genetics
RNA, Ribosomal metabolism
Ataxia Telangiectasia Mutated Proteins metabolism
Carrier Proteins metabolism
Cell Nucleolus genetics
DNA, Ribosomal genetics
DNA-Binding Proteins metabolism
Nuclear Proteins metabolism
Phosphoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31913317
- Full Text :
- https://doi.org/10.1038/s41467-019-13981-x