title: Cdc15 Phosphorylates the C-terminal Domain of RNA Polymerase II for Transcription during Mitosis.
abstract: In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1, and Ctk1) and phosphatases (Ssu72, Rtr1, and Fcp1), which act through the post-translational modification of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. The CTD comprises the repeated Tyr-Ser-Pro-Thr-Ser-Pro-Ser motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase(s) and its role in transcription remains unknown. Here we have identified Cdc15 as a potential kinase phosphorylating Ser-2 and Ser-5 of CTD for transcription during mitosis in the budding yeast. The phosphorylation of CTD by Cdc15 is independent of any prior Ser phosphorylation(s). The inactivation of Cdc15 causes reduction of global CTD phosphorylation during mitosis and affects the expression of genes whose transcript levels peak during mitosis. Cdc15 also influences the complete transcription of clb2 gene and phosphorylates Ser-5 at the promoter and Ser-2 toward the 3' end of the gene. The observation that Cdc15 could phosphorylate Ser-5, as well as Ser-2, during transcription in mitosis is in contrast to the phosphorylation marks put by the kinases in interphase (G1, S, and G2), where Cdck7/Kin28 phosphorylates Ser-5 at promoter and Bur1/Ctk1 phosphorylates Ser-2 at the 3' end of the genes.
authors.affiliation: From the Molecular and Structural Biology Division.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: the Microbiology Division, and.
authors.forename: Shivangi
authors.initials: S
authors.lastname: Rastogi
authors.affiliation: From the Molecular and Structural Biology Division.
authors.forename: Harish
authors.initials: H
authors.lastname: Shukla
authors.affiliation: From the Molecular and Structural Biology Division.
authors.forename: Mohd
authors.initials: M
authors.lastname: Asalam
authors.affiliation: the Toxicology Division, Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow PIN 226 031, India and.|the Academy of Scientific and Innovative Research, New Delhi 110025, India.
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: From the Molecular and Structural Biology Division, sohail@cdri.res.in.|the Academy of Scientific and Innovative Research, New Delhi 110025, India.
authors.forename: Md Sohail
authors.initials: MS
authors.lastname: Akhtar
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019926:Cyclin B / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C082279:CDC15 protein; C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D019204:GTP-Binding Proteins
keywords: C-terminal domain (C-terminal tail domain, CTD); RNA polymerase II; chromatin; cyclin-dependent kinase 7 (CDK7); gene regulation; mRNA; transcription