Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage.
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.
Napolitano
Giuliana
G
Department of Structural and Functional Biology, University of Naples Federico II, Naples, Italy.
Amente
Stefano
S
Castiglia
Virginia
V
Gargano
Barbara
B
Ruda
Vera
V
Darzacq
Xavier
X
Bensaude
Olivier
O
Majello
Barbara
B
Lania
Luigi
L
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
D017411:Ribonucleoproteins, Small Nuclear; D002110:Caffeine; D042925:Positive Transcriptional Elongation Factor B; D004257:DNA Polymerase II