Caffeine prevents transcription inhibition and P-TEFb/ 7SK dissociation following UV-induced DNA damage

Giuliana Napolitano, Stefano Amente, Virginia Castiglia, Barbara Gargano, Vera Ruda, Xavier Darzacq, Olivier Bensaude, Barbara Majello, Luigi Lania

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. Methodology/Principal Findings: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. Conclusion/Significance: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated.

Original languageEnglish
Article numbere11245
JournalPLoS One
Volume5
Issue number6
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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