The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage
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The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. / Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A; Gwerder, Myriam; Gutsche, Katrin; Altmeyer, Matthias; Jungmichel, Stephanie; Toledo Lazaro, Luis Ignacio; Fink, Daniel; Rask, Maj-Britt; Grøfte, Merete; Lukas, Claudia; Nielsen, Michael L; Smerdon, Stephen J; Lukas, Jiri; Stucki, Manuel.
In: Nature Cell Biology, Vol. 16, No. 8, 08.2014, p. 792-803.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
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
VL - 16
SP - 792
EP - 803
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 8
ER -
ID: 122495483