Anatomy and Cell Biology 4411B Lecture Notes - Cyclin-Dependent Kinase 2, Hepatocyte, Cytostasis
23 May 2012
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Most researchers now agree that this represents not just a very slow g1 phase but a distinct phase outside the normal cell cycle: g0 - non-proliferative state that may last hours or days. Once rb is phosphory- lated, the restriction point is passed: prb releases e2f. E2f causes the transcription of cyclin a and cdc6. Cyclin a phosphorylates e2f to degrade it in a negative feedback. At the s phase, cyclin a phosphory- lates cdc6 so that is cannot be degraded. Cdc6 gets local- ized to the cytosol after this so that dna cannot be replicat- ed again: in early g1, cdc6 interacts with orc and loads the mcm proteins onto chromatin. The assembly of orc, cdc6, and mcm proteins into pre-replicative complexes makes chromatin competent or li- censed for replication: cdc6 and mcm are down-regulated in quiescent, terminal differ- entiated cells and senescent cells.
