A role for the TFIIH XPB DNB helicase in promoter escape by RNA polymeraseII

TFIIH is an RNA polymerase II transcription factor that performs ATP-depend ent functions in both transcription initiation, where it catalyzes formatio n of the open complex, and in promoter escape, where it suppresses arrest o f the early elongation complex at promoter-proximal sites. TFIIH possesses three known ATP-dependent activities: a 3' -->5' DNA helicase catalyzed by its XPB subunit, a 5' --> 3' DNA helicase catalyzed by its XPD subunit, and a carboxyl-terminal domain (CTD) kinase activity catalyzed by its CDK7 sub unit. In this report, we exploit TFIIH mutants to investigate the contribut ions of TFIIH DNA helicase and CTD kinase activities to efficient promoter escape by RNA polymerase II in a minimal transcription system reconstituted with purified polymerase and general initiation factors. Our findings argu e that the TFIIH XPB DNA helicase is primarily responsible for preventing p remature arrest of early elongation intermediates during exit of polymerase from the promoter.