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S phase
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==Regulation== {{Main|G1/S transition}} Entry into S-phase is controlled by the G1 [[restriction point]] (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling.<ref name=":6">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK6318/|title=The Restriction Point of the Cell Cycle|last1=Pardee|first1=Arthur B.|last2=Blagosklonny|first2=Mikhail V. | name-list-style = vanc |date=2013|publisher=Landes Bioscience}}</ref> This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable.<ref name=":6" /> Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3 [[cyclin]], which complexes with the [[Cyclin-dependent kinase|cyclin dependent kinase]] CDK2.<ref name=":7">{{cite journal | vauthors = Bertoli C, Skotheim JM, de Bruin RA | title = Control of cell cycle transcription during G1 and S phases | journal = Nature Reviews. Molecular Cell Biology | volume = 14 | issue = 8 | pages = 518β28 | date = August 2013 | pmid = 23877564 | pmc = 4569015 | doi = 10.1038/nrm3629 }}</ref> The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating the transcriptional repressor [[Whi5]].<ref name=":7" /> Since upregulation of S-phase genes drive further suppression of [[Whi5]], this pathway creates a positive feedback loop that fully commits cells to S-phase gene expression.<ref name=":7" /> A remarkably similar regulatory scheme exists in mammalian cells.<ref name=":7" /> [[Mitogen]]ic signals received throughout G1-phase cause gradual accumulation of cyclin D, which complexes with CDK4/6.<ref name=":7" /> Active cyclin D-CDK4/6 complex induces release of [[E2F]] transcription factor, which in turn initiates expression of S-phase genes.<ref name=":7" /> Several E2F target genes promote further release of E2F, creating a positive feedback loop similar to the one found in yeast.<ref name=":7" />
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