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

The NNF Center for Protein Research

34 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Genes & Development
Vol/bind	28
Udgave nummer	18
Sider (fra-til)	1977-1982
Antal sider	6
ISSN	0890-9369
DOI	https://doi.org/10.1101/gad.246272.114
Status	Udgivet - 15 sep. 2014

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10.1101/gad.246272.114

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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.

U2 - 10.1101/gad.246272.114

DO - 10.1101/gad.246272.114

M3 - Journal article

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SN - 0890-9369

VL - 28

SP - 1977

EP - 1982

JO - Genes & Development

JF - Genes & Development

IS - 18

ER -

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

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