title: Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated.
authors.affiliation: Department of Structural and Functional Biology, University of Naples Federico II, Naples, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Napolitano
authors.forename: Stefano
authors.initials: S
authors.lastname: Amente
authors.forename: Virginia
authors.initials: V
authors.lastname: Castiglia
authors.forename: Barbara
authors.initials: B
authors.lastname: Gargano
authors.forename: Vera
authors.initials: V
authors.lastname: Ruda
authors.forename: Xavier
authors.initials: X
authors.lastname: Darzacq
authors.forename: Olivier
authors.initials: O
authors.lastname: Bensaude
authors.forename: Barbara
authors.initials: B
authors.lastname: Majello
authors.forename: Luigi
authors.initials: L
authors.lastname: Lania
mesh_terms: D002110:Caffeine / Q000494:pharmacology*; D004249:DNA Damage; D004257:DNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D017411:Ribonucleoproteins, Small Nuclear; D002110:Caffeine; D042925:Positive Transcriptional Elongation Factor B; D004257:DNA Polymerase II