TFIIH controls developmentally-regulated cell cycle progression as a holocomplex.
Basal transcription factor, TFIIH, is a multifunctional complex that carries out not only transcription but also DNA repair and cell cycle control. TFIIH is composed of two sub-complexes: core TFIIH and Cdk-activating kinase (CAK). In vitro studies suggest that CAK is sufficient for cell cycle regulation, whereas core TFIIH is required for DNA repair. However, the TFIIH complexes that perform these functions in vivo have yet to be identified. Here, we perform an in vivo dissection of TFIIH activity by characterizing mutations in a core subunit p52 in Drosophila. p52 mutants are hypersensitive to UV, suggesting a defect in DNA repair. Nonetheless, mutant cells are able to divide and express a variety of differentiation markers. Although p52 is not essential for cell cycle progression itself, p52 mutant cells in the eye imaginal disc are unable to synchronize their cell cycles and remain arrested at G1. Similar cell cycle phenotypes are observed in mutations in another core subunit XPB and a CAK-component CDK7, suggesting that defects in core TFIIH affect the G1/S transition through modification of CAK activity. We propose that during development the function of TFIIH as a cell cycle regulator is carried out by holo-TFIIH.
Matsuno
Motomi
M
Department of Developmental Genetics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Kose
Hiroyuki
H
Okabe
Masataka
M
Hiromi
Yasushi
Y
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020035:Holoenzymes / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D029721:Drosophila Proteins; D020035:Holoenzymes; C520555:mrn protein, Drosophila; D051758:Transcription Factor TFIIH; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase