Lect10_CellCycle3

Lect10_CellCycle3 - M (mitotic) Phase Phase involves...

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Phase involves mitosis and cytokinesis . Chromosomes and cytoplasm are partitioned into daughter cells. Chromosome separation is controlled by metaphase checkpoint (aka spindle assembly checkpoint) , which delays the onset of sister chromatid separation until all chromosomes are correctly aligned on the mitotic spindle. If cell is unprepared for mitosis, cell blocks metaphase - anaphase transition (hence term metaphase checkpoint). 1 M (mitotic) Phase Bio 103-Fall 2009 © Steven Gross
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M-CDK phosphorylates Securin, targeting it for destruction, and allowing chromosome separation Bio 103-Fall 2009 © Steven Gross M-cdk phosphorylates histone H1, triggering chromosome condensation Dissasembly of nuclear lamina
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Control of M-CDK activity M-Cyclin made during interphase, especially increasing in G2 and M phase, leading to an increase in M-CDK complexes. M-CDK complex initially inactive, due to Wee1 (inactivating kinase). . 3 Bio 103-Fall 2009 © Steven Gross
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Regulation of M-CDK activity via protein-protein interaction and phosphorylation CDKs require cyclins for activation. CDK-activating kinase ( CAK ) is also required for activation of cyclin:CDK complexes. Wee1 ( inactivating kinase ) and Cdc25 ( activating phosphatase ) help regulate activation of M-cyclin-CDKs . Note that active M-CDK can enhance its own activation by phosphorylating and thereby activating Cdc25 - example of positive feedback loop that generates rapid activation . 4 Bio 103-Fall 2009 © Steven Gross p42 MAPK
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How does mitosis end? Regulation of Anaphase promoting complex (APC), which controls degradation of mitotic cyclins and exit from mitosis cyclins targeted for destruction by covalent addition of multiple ubiquitin molecules. Cyclins contain a destruction box ( amino acid sequence) , recognized by the ubiquitin E3 ligase APC . Cdh1 targets APC to cyclins, but is initially inactive due to phosphorylation by G1-CDK In late anaphase Cdh1 is activated (dephosphorylated) by phosphatase (Cdc14). Spindle position checkpoint prevents Cdc14 from becoming active until after all chromosomes have completed separation. Note - APC also functioned earlier to initiate anaphase by ubiquitylating securin, although here APC is regulated by a different co- factor called Cdc20 ). Bio 103-Fall 2009 © Steven Gross
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Summary: critical events controlled by each cyclin-CDK complex G1-CDK and G1/S-CDK: a. phosphorylate Rb release transcription factor E2F transcription of S-phase genes make S-cyclin protein and others for (e.g. ) DNA synthesis b. phosphorylate Sic1 (a CKI that blocks S-Cdk activity) Sic1 recognized and targeted for destruction by SCF S-CdK activated S-CDK a. Initiate DNA replication by phosphorylating Cdc6, releasing it from DNA OR and allowing replication to start. This phosphorylation also targets Cdc6 for destruction. M-CDK
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This note was uploaded on 12/13/2011 for the course BIOSCI d103 taught by Professor Staff during the Fall '11 term at UC Irvine.

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Lect10_CellCycle3 - M (mitotic) Phase Phase involves...

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