Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation
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...
| Glavni autori: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
Nature Research
2020
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| _version_ | 1826302646945841152 |
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| author | Mooser, C Symeonidou, I Leimbacher, P Ribeiro, A Shorrocks, A Jungmichel, S Larsen, S Knechtle, K Jasrotia, A Zurbriggen, D Jeanrenaud, A Leikauf, C Fink, D Nielsen, M Blackford, A Stucki, M |
| author_facet | Mooser, C Symeonidou, I Leimbacher, P Ribeiro, A Shorrocks, A Jungmichel, S Larsen, S Knechtle, K Jasrotia, A Zurbriggen, D Jeanrenaud, A Leikauf, C Fink, D Nielsen, M Blackford, A Stucki, M |
| author_sort | Mooser, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:50:45Z |
| format | Journal article |
| id | oxford-uuid:e8ce3708-cfa5-4ef8-9b5a-b67a2a725e00 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:50:45Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:e8ce3708-cfa5-4ef8-9b5a-b67a2a725e002022-03-27T10:49:26ZTreacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e8ce3708-cfa5-4ef8-9b5a-b67a2a725e00EnglishSymplectic Elements at OxfordNature Research2020Mooser, CSymeonidou, ILeimbacher, PRibeiro, AShorrocks, AJungmichel, SLarsen, SKnechtle, KJasrotia, AZurbriggen, DJeanrenaud, ALeikauf, CFink, DNielsen, MBlackford, AStucki, MInduction 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. |
| spellingShingle | Mooser, C Symeonidou, I Leimbacher, P Ribeiro, A Shorrocks, A Jungmichel, S Larsen, S Knechtle, K Jasrotia, A Zurbriggen, D Jeanrenaud, A Leikauf, C Fink, D Nielsen, M Blackford, A Stucki, M Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title | Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title_full | Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title_fullStr | Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title_full_unstemmed | Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title_short | Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation |
| title_sort | treacle controls the nucleolar response to rdna breaks via topbp1 recruitment and atr activation |
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