Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription

• DOI: 10.1038/srep00189
• Publication Date: 2011-12-12T17:19:46Z
• Authors: María Guillamot; Eusebio Manchado; Massimo Chiesa; Gonzalo Gómez-López; David G. Pisano; María P. Sacristán; Marcos Malumbres
• Keywords: Transcriptional Activation; 0301 basic medicine; Transcription, Genetic; 2407 Biología Celular; 2415 Biología Molecular; Mitosis; Article; Gene Expression Regulation, Enzymologic; Epigenesis, Genetic; Phosphates; Mice; 03 medical and health sciences; 2302 Bioquímica; Animals; Phosphorylation; Alleles; Cells, Cultured; Binding Sites; Cell Cycle; Phosphatases; Exons; Fibroblasts; 3. Good health; Dual-Specificity Phosphatases; RNA Polymerase II; Transcription

Cdc14 is an essential phosphatase in yeast but its role in the mammalian cell cycle remains obscure. We report here that Cdc14b-knockout cells display unscheduled induction of multiple cell cycle regulators resulting in early entry into DNA replication and mitosis from quiescence. Cdc14b dephosphorylates Ser5 at the C-terminal domain (CTD) of RNA polymerase II, a major substrate of cyclin-dependent kinases. Lack of Cdc14b results in increased CTD-Ser5 phosphorylation, epigenetic modifications that mark active chromatin, and transcriptional induction of cell cycle regulators. These data suggest a function for mammalian Cdc14 phosphatases in the control of transcription during the cell cycle.