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

The NNF Center for Protein Research

78 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Cell Biology
Vol/bind	16
Udgave nummer	8
Sider (fra-til)	792-803
Antal sider	12
ISSN	1465-7392
DOI	https://doi.org/10.1038/ncb3007
Status	Udgivet - aug. 2014

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10.1038/ncb3007

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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, bind 16, nr. 8, s. 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.",

author = "Larsen, {Dorthe H} and Flurina Hari and Clapperton, {Julie A} and Myriam Gwerder and Katrin Gutsche and Matthias Altmeyer and Stephanie Jungmichel and {Toledo Lazaro}, {Luis Ignacio} and Daniel Fink and Maj-Britt Rask and Merete Gr{\o}fte and Claudia Lukas and Nielsen, {Michael L} and Smerdon, {Stephen J} and Jiri Lukas and Manuel Stucki",

year = "2014",

month = aug,

doi = "10.1038/ncb3007",

language = "English",

volume = "16",

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issn = "1465-7392",

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T1 - The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

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

Y1 - 2014/8

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.

U2 - 10.1038/ncb3007

DO - 10.1038/ncb3007

M3 - Journal article

C2 - 25064736

SN - 1465-7392

VL - 16

SP - 792

EP - 803

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -

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

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