Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription

Abstract

This work is licensed under a Creative Commons Attribution-NonCommercial. ; 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. ; This work was funded by grants from the Association for International Cancer Research (AICR #08-0188), Foundation Ramón Areces, and the Spanish Ministry of Science and Innovation (MICINN; BFU2008-04293 to M.S.; SAF2009-07973 to M.M.). The Cell Division and Cancer Group of the CNIO is supported by the OncoCycle Programme (S-BIO-0283-2006) from the Comunidad de Madrid, the OncoBIO Consolider-Ingenio 2010 Programme (CSD2007- 00017) from the MICINN, Madrid, and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548). ; Peer Reviewed