title: Cell cycle adaptations of embryonic stem cells.
abstract: ES cells proliferate with very short gap phases yet maintain their capacity to differentiate. It had been thought that the levels of cyclins and other substrates of ubiquitin ligase APC/C remain nearly constant and Cdk activity remains constitutively high in mouse ES cells. Here we demonstrate that APC/C (anaphase-promoting complex/cyclosome) enzyme is active in ES cells but attenuated by high levels of the Emi1 (early mitotic inhibitor-1) protein. Despite the presence of high Cdk activity during the G1 phase, chromatin can be effectively licensed for DNA replication and fast entry into the S phase can still occur. High Cdk activity during S-G2-M phases produces high levels of the DNA replication factor Cdt1, and this leads to efficient Mcm proteins loading on chromatin after mitotic exit. Although disturbing the usual balance between Cdk activity and APC/C activity found in somatic cells, a few key adaptations allow normal progression of a very rapid cell cycle.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabeni
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.forename: Paul H
authors.initials: PH
authors.lastname: Lerou
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000502:physiology*; D005434:Flow Cytometry; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C498961:Fbxo5 protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2
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