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

Dorthe H Larsen; Flurina Hari; Julie A Clapperton; Myriam Gwerder; Katrin Gutsche; Matthias Altmeyer; Stephanie Jungmichel; Luis Ignacio Toledo Lazaro; Daniel Fink; Maj-Britt Rask; Merete Grøfte; Claudia Lukas; Michael L Nielsen; Stephen J Smerdon; Jiri Lukas; Manuel Stucki

doi:10.1038/ncb3007

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

Dorthe H Larsen, Flurina Hari, Julie A Clapperton, Myriam Gwerder, Katrin Gutsche, Matthias Altmeyer, Stephanie Jungmichel, Luis Ignacio Toledo Lazaro, Daniel Fink, Maj-Britt Rask, Merete Grøfte, Claudia Lukas, Michael L Nielsen, Stephen J Smerdon, Jiri Lukas, Manuel Stucki

Novo Nordisk Foundation Center for Protein Research

78 Citations (Scopus)

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.

Original language	English
Journal	Nature Cell Biology
Volume	16
Issue number	8
Pages (from-to)	792-803
Number of pages	12
ISSN	1465-7392
DOIs	https://doi.org/10.1038/ncb3007
Publication status	Published - Aug 2014

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Larsen, D. H., Hari, F., Clapperton, J. A., Gwerder, M., Gutsche, K., Altmeyer, M., Jungmichel, S., Toledo Lazaro, L. I., Fink, D., Rask, M-B., Grøfte, M., Lukas, C., Nielsen, M. L., Smerdon, S. J., Lukas, J., & Stucki, M. (2014). The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. Nature Cell Biology, 16(8), 792-803. https://doi.org/10.1038/ncb3007

Larsen, DH, Hari, F, Clapperton, JA, Gwerder, M, Gutsche, K, Altmeyer, M, Jungmichel, S, Toledo Lazaro, LI, Fink, D, Rask, M-B, Grøfte, M, Lukas, C , Nielsen, ML, Smerdon, SJ, Lukas, J & Stucki, M 2014, 'The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage', Nature Cell Biology, vol. 16, no. 8, pp. 792-803. https://doi.org/10.1038/ncb3007

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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.",

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doi = "10.1038/ncb3007",

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AU - Larsen, Dorthe H

AU - Hari, Flurina

AU - Clapperton, Julie A

AU - Gwerder, Myriam

AU - Gutsche, Katrin

AU - Altmeyer, Matthias

AU - Jungmichel, Stephanie

AU - Toledo Lazaro, Luis Ignacio

AU - Fink, Daniel

AU - Rask, Maj-Britt

AU - Grøfte, Merete

AU - Lukas, Claudia

AU - Nielsen, Michael L

AU - Smerdon, Stephen J

AU - Lukas, Jiri

AU - Stucki, Manuel

PY - 2014/8

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N2 - 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.

AB - 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.

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DO - 10.1038/ncb3007

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VL - 16

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JO - Nature Cell Biology

JF - Nature Cell Biology

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ER -

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

Abstract

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