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

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

  • Genes Dev. 2014 Sep 15;28(18):1977-82. doi: 10.1101/gad.246272.114.
Melanie Blasius 1,  Sebastian A Wagner 2,  Chunaram Choudhary 2,  Jiri Bartek 3,  Stephen P Jackson 4
Affiliations

Affiliations

  • 1 The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Genome Integrity Unit, Danish Cancer Society Research Centre, 2100 Copenhagen, Denmark;
  • 2 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark;
  • 3 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Institute of Molecular and Translational Medicine, Palacky University, 77900 Olomouc, Czech Republic;
  • 4 The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, United Kingdom; The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom [email protected] [email protected].
PMID: 25189701 DOI: 10.1101/gad.246272.114
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.

Keywords

14-3-3; DNA damage response; MAPKAPK2; UV; nuclear exosome.

Figures