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LET'S TALK LIFE-SCIENCE CELL BIOLOGY

Suraj Prakash Sharma | Ekta Chotia

CELL CYCLE
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5.6.         Metaphase to anaphase transition:

Model of the regulation of mitosis and G1 by APC-dependent cyclin proteolysis. The first phase of cyclin B1/Clb2 proteolysis by APCCdc20 mediates spindle disassembly and cytokinesis. APCCdc20-dependent degradation of cyclin A2/Clb5 leads to activation of Cdh1 and in yeast of the CKI Sic1 downregulating mitotic kinase activity in G1. Whether there is any role of human CKIs such as p21 or p27 in this context has to be defined. APCCdh1 inactivates cyclin B1/Clb2 further during mitotic exit and the G1 phase of the cell cycle to regulate cell growth and the length of G1 allowing cell differentiation and correct assembly of pre-RCs at origins of replication and subsequent complete and accurate DNA replication

Metaphase Cyclin A is degraded and at the termination of mitosis Cyclin B is degraded.

Regulation of cell cycle progression by APC/C-dependent proteolysis. (A) Sister chromatid separation and Cdk1 inactivation both depend on APC/CCdc20. Activation of APC/CCdc20 but not APC/CCdh1 requires phosphorylation of core subunits by Cdk1–cyclin B. APC/CCdc20 mediates sister chromatid separation and Cdk1 inactivation by degrading securins and B-type cyclins, respectively. APC/CCdc20also creates the conditions that keep Cdk1–cyclin B complexes inactive during the ensuing G1 phase. Cdk1 inactivation by APC/CCdc20 permits release from its inhibitor of the Cdc14 phosphatase which, by dephosphorylating Sic1 and Cdh1, causes accumulation of a CKI and activation of APC/CCdh1. Broken lines indicate proteolysis and P in a circle indicates phosphorylation. (B) Changes in the abundance and activity of CDKs, the securin Pds1, the CKI Sic1, and both forms of the APC/C during the cell cycle.

Anaphase is the stage of mitosis or meiosis when chromosomes are split and the sister chromatids move to opposite poles of the cell. During metaphase, APC/C is inhibited until all the sister kinetochores are attached to opposite poles of the  mitotic spindle. When all the kinetochores are properly attached, APC/C becomes active and promotes binding to cdc20. M cyclins and securin are then targeted for degradation through ubiqutylation by APC/Ccdc20 leading to the onset of anaphase stage. Pds1p control the transition from  Metaphase to anaphase.CDC20 is required to degrade the pds1p.

5.7.         M to G1 transition :

After the completion  of mitosis,  the entry into another round of mitosis is prevented by inhibiting Cdk activity. During the transition from metaphase to anaphase, Cdh1 is phosphorylated by M-Cdk and thus prevent it from attaching to APC/C. As the M-Cdk is degraded in later stage of mitosis, cdc20 gets released and Cdh1 can bind to APC/C, thus keeping it activated for the M/  G1transition. Cdh1 is necessary for APC to degrade the Cyclin B. Degradation of Cyclin B is mark of exit of Mitosis.

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