L15 - • PROBLEM SET ON CELL CYCLE IS ON THE WEB (2 PS...

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Unformatted text preview: • PROBLEM SET ON CELL CYCLE IS ON THE WEB (2 PS SINCE THE EXAM) • THE EXAM KEY IS ON THE WEB • For next lecture: Chapter 4 pages:200-209 mostly review 209-219; 222-228; 241-245 Genetic (and biochemical) analysis of the cell cycle led to identification of a highly conserved central control system for the cell cycle. Cyclin-dependent kinase(s)(Cdk) associates successively with different cyclins to trigger different events of the cycle. For simplicity only a single Cdk is shown and only two cyclins--much more complicated than this. Once Cdks are activated, they phosphorylate many different proteins to induce the events of each cell cycle stage. Once Cdks have completed their tasks, the cyclin subunits are destroyed by proteolysis, Cdks revert to inactivity until activated at the next cell cycle stage. Activation of M-phase Cyclin-Cdk Complexes (M-Cdk) Triggers Entry into Mitosis M-Cdk (in complex with cyclin) gets stock-piled in G2. It has been phosphorylated by CAK and is primed and ready to act. But, its activity is suppressed by Wee1 kinase (remember 2 inhibitory phosphates). Protein phosphatase Cdc25 supplies the crucial activating event when it removes these inhibitory phosphates, allowing M-Cdk to function. Cdc25 is activated by a kinase called Polo kinase (not shown in the cartoon) and then by M-Cdk itself as positive feed-back. M-Cdk also feedbacks and inhibits its own inhibitor Wee1 kinase. Remember cohesion from the last lecture; it attaches chromatids at the centromere Anaphase begins with the sudden disruption of this cohesion. 1 2 3 4 APC Initiates Sister Chromatid Separation by initiating the proteolysis of securin. (1) Cdc20 activates APC by a poorly understood mechanism. (2) APC ubiquitinates securin, leading to its destruction. (3) Securin had been holding separase in an inactive complex. Now separase is ACTIVE. (4) Separase cleaves the cohesin complex that holds the sister chromatids together. There is a Control System that Mediates Cell Cycle Arrest and Specific Check Points 2) Trigger mitosis machinery to assemble the mitotic spindle 3) Trigger anaphase and proceed to cytokinesis 1) Trigger cell cycle entry and chromosome duplication There is a control system comprised of sensors that determine whether the required events have occurred appropriately before releasing the cell into the next stage of the cycle The places where these sensors function in the cell cycle are called checkpoints . If events have not occurred properly, the cell cycle will arrest at this stage and proceed NO FURTHER For example, a G1 checkpoint monitors for DNA damage and if present arrests the cell cycle in G1 The G1 checkpoint blocks progression into S-phase (DNA replication) by inhibiting the progression of the G1/S- Cdk and S-Cdk complexes....
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This note was uploaded on 03/28/2010 for the course MCD BIO 110 taught by Professor Hinck during the Fall '09 term at University of California, Santa Cruz.

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L15 - • PROBLEM SET ON CELL CYCLE IS ON THE WEB (2 PS...

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