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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.

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.

SUBMITTER: Napolitano G 

PROVIDER: S-EPMC2888590 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Napolitano Giuliana G   Amente Stefano S   Castiglia Virginia V   Gargano Barbara B   Ruda Vera V   Darzacq Xavier X   Bensaude Olivier O   Majello Barbara B   Lania Luigi L  

PloS one 20100621 6


<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We show here  ...[more]

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