Budding yeast CTDK-I is required for DNA damage-induced transcription.
CTDK-I phosphorylates the C-terminal domain (CTD) of the large subunit of yeast RNA polymerase II in a reaction that stimulates transcription elongation. Mutations in CTDK-I subunits-Ctk1p, Ctk2p, and Ctk3p-confer conditional phenotypes. In this study, we examined the role of CTDK-I in the DNA damage response. We found that mutation of individual CTDK-I subunits rendered yeast sensitive to hydroxyurea (HU) and UV irradiation. Treatment with DNA-damaging agents increased phosphorylation of Ser2 within the CTD repeats in wild-type but not in ctk1Delta mutant cells. Using microarray hybridization, we identified genes whose transcription following DNA damage is Ctk1p dependent, including several DNA repair and stress response genes. Following HU treatment, the level of Ser2-phosphorylated RNA polymerase II increased both globally and on the CTDK-I-regulated genes. The pleiotropic phenotypes of ctk mutants suggest that CTDK-I activity is essential during large-scale transcriptional repatterning under stress and unfavorable growth conditions.
Ostapenko
Denis
D
Department of Molecular Biophysics, Yale University School of Medicine, New Haven, Connecticut 06520-8024, USA.
Solomon
Mark J
MJ
D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006918:Hydroxyurea / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011494:Protein Kinases / Q000172:deficiency* / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects
D012694:Serine; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D012319:RNA Polymerase II; D006918:Hydroxyurea