A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

Melanie Blasius; Sebastian A Wagner; Chuna Ram Choudhary; Jiri Bartek; Stephen P Jackson

doi:10.1101/gad.246272.114

A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

Melanie Blasius, Sebastian A Wagner, Chuna Ram Choudhary, Jiri Bartek, Stephen P Jackson

Novo Nordisk Foundation Center for Protein Research

34 Citations (Scopus)

Abstract

RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.

Original language	English
Journal	Genes & Development
Volume	28
Issue number	18
Pages (from-to)	1977-1982
Number of pages	6
ISSN	0890-9369
DOIs	https://doi.org/10.1101/gad.246272.114
Publication status	Published - 15 Sept 2014

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title = "A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response",

abstract = "RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.",

author = "Melanie Blasius and Wagner, {Sebastian A} and Choudhary, {Chuna Ram} and Jiri Bartek and Jackson, {Stephen P}",

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T1 - A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

AU - Blasius, Melanie

AU - Wagner, Sebastian A

AU - Choudhary, Chuna Ram

AU - Bartek, Jiri

AU - Jackson, Stephen P

PY - 2014/9/15

Y1 - 2014/9/15

N2 - RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.

AB - RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome targeting (NEXT) complex that regulates turnover of noncoding RNAs termed promoter upstream transcripts (PROMPTs). We show that the NEXT subunit RBM7 is phosphorylated upon DNA damage by the MAPKAPK2 kinase and establish that this mediates 14-3-3 binding and decreases PROMPT binding. These findings and our observation that cells lacking RBM7 display DNA damage hypersensitivity link PROMPT turnover to the DNA damage response.

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DO - 10.1101/gad.246272.114

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EP - 1982

JO - Genes & Development

JF - Genes & Development

IS - 18

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A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

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