Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes

Ian R. Powley, Alexander Kondrashov, Lucy A. Young, Helen C. Dobbyn, Kirsti Hill, Ian G. Cannell, Mark Stoneley, Yi Wen Kong, Julia A. Cotes, Graeme C.M. Smith, Ron Wek, Christopher Hayes, Timothy W. Gant, Keith A. Spriggs, Martin Bushell, Anne E. Willis

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

UVB-induced lesions in mammalian cellular DNA can, through the process of mutagenesis, lead to carcinogenesis. However, eukaryotic cells have evolved complex mechanisms of genomic surveillance and DNA damage repair to counteract the effects of UVB radiation. We show that following UVB DNA damage, there is an overall inhibition of protein synthesis and translational reprogramming. This reprogramming allows selective synthesis of DDR proteins, such as ERCC1, ERCC5, DDB1, XPA, XPD, and OGG1 and relies on upstream ORFs in the 5′ untranslated region of these mRNAs. Experiments with DNA-PKcs-deficient cell lines and a specific DNA-PKcs inhibitor demonstrate that both the general repression of mRNA translation and the preferential translation of specific mRNAs depend on DNA-PKcs activity, and therefore our data establish a link between a key DNA damage signaling component and protein synthesis.

Original languageEnglish (US)
Pages (from-to)1207-1220
Number of pages14
JournalGenes and Development
Volume23
Issue number10
DOIs
StatePublished - May 15 2009

Keywords

  • DNA damage
  • Translation
  • Upstream ORF

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes'. Together they form a unique fingerprint.

  • Cite this

    Powley, I. R., Kondrashov, A., Young, L. A., Dobbyn, H. C., Hill, K., Cannell, I. G., Stoneley, M., Kong, Y. W., Cotes, J. A., Smith, G. C. M., Wek, R., Hayes, C., Gant, T. W., Spriggs, K. A., Bushell, M., & Willis, A. E. (2009). Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes. Genes and Development, 23(10), 1207-1220. https://doi.org/10.1101/gad.516509