title: The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II.
abstract: CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet and School of Technology and Health, Royal Institute of Technology, Novum, SE-141 87 Huddinge, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Elmlund
authors.forename: Vera
authors.initials: V
authors.lastname: Baraznenok
authors.forename: Martin
authors.initials: M
authors.lastname: Lindahl
authors.forename: Camilla O
authors.initials: CO
authors.lastname: Samuelsen
authors.forename: Philip J B
authors.initials: PJ
authors.lastname: Koeck
authors.forename: Steen
authors.initials: S
authors.lastname: Holmberg
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
mesh_terms: D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D020035:Holoenzymes; D029702:Schizosaccharomyces pombe Proteins; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; C112462:srb10 protein, S pombe; D012319:RNA Polymerase II