Chapter 17 The Cell Cycle
Jen-Hsuan Wei
Lab/Office: N214, IMB Email: [email protected] Outline
1. Overview of the Cell Cycle 2. The Cell Cycle Control System - Cdk Cdk Activation - Cyclin, Activating Kinase CAK, Cdc25 Cdk Inactivation - CKI, Inhibitory Kinase Wee1 Proteolysis of Cyclin and CKI - APC/C and SCF 3. Distinct Stages of M Phase Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis 4. Cell Cycle Checkpoints DNA Damage Checkpoint Spindle Assembly Checkpoint Overview of the Cell Cycle Introduction Introduction Introduction The Eukaryotic Cell Cycle Usually Consists of Four Phases Cell-Cycle Progression Can Be Studied in Various Ways Cell-Cycle Progression Can Be Studied in Various Ways Cell-Cycle Progression Can Be Studied in Various Ways Cell-Cycle Progression Can Be Studied in Various Ways The Cell Cycle Control System The Cell-Cycle Control System Triggers the Major Events of the Cell Cycle https://educationalgames.nobelprize.org/educational/medicine/2001/cellcycle.html Driving Force of the Cell Cycle - Cdk The Cell-Cycle Control System Depends on Cyclically Activated Cyclin- Dependent Protein Kinases (Cdks) The Cell-Cycle Control System Depends on Cyclically Activated Cyclin- Dependent Protein Kinases (Cdks) The Cell-Cycle Control System Depends on Cyclically Activated Cyclin- Dependent Protein Kinases (Cdks) Cdk Activation - Cyclin, Activating Kinase The Cell-Cycle Control System Depends on Cyclically Activated Cyclin- Dependent Protein Kinases (Cdks) Cdk Inactivation - CKI, Inhibitory Kinase Cdk Activity Can Be Suppressed By Inhibitory Phosphorylation and Cdk Inhibitor Proteins (CKIs) Cdk Activity Can Be Suppressed By Inhibitory Phosphorylation and Cdk Inhibitor Proteins (CKIs) The Cell-Cycle Control System Depends on Cyclically Activated Cyclin- Dependent Protein Kinases (Cdks) Proteolysis of Cyclin and CKI Regulated Proteolysis Triggers the Metaphase-to-Anaphase Transition
APC/C Targets: (1) Securin (2) M-cyclin Regulated Proteolysis Regulates the G1-to-S Transition
SCF Targets: (1) CKI (2) G1/S-cyclin FUCCI - Fluorescent Ubiquitination-Based Cell Cycle Indicator FUCCI - Fluorescent Ubiquitination-Based Cell Cycle Indicator M Phase - M-Cdk Dephosphorylation Activates M-Cdk at the Onset of Mitosis Break Key Cellular Structures in Mitosis
1. Chromosomes
2. Centrosomes
3. Microtubule-based Spindle Chromosomes in S Phase Cohesins Hold Sister Chromatids Together Chromosomes in M Phase Condensin Helps Configure Duplicated Chromosomes for Separation Condensin Helps Configure Duplicated Chromosomes for Separation Cohesins and Condensins during the cell cycle
Skibbens, JCS 2019 132: jcs220491 doi: 10.1242/ Centrosomes Centrosomes at the Poles of the Mitotic Spindle Centrosome Duplication Occurs Early in the Cell Cycle Distinct Stages of M Phase Overview of Mitosis Mitosis (DIC Imaging) Mitosis (Phase-Contrast Imaging) Prophase Mitosis - Prophase Prometaphase Mitosis - Prometaphase Spindle - Machinery for Cell Division The Mitotic Spindle Is a Microtubule-Based Machine Centrosome-Driven Spindle Assembly Microtubule-Dependent Motor Proteins Govern Spindle Assembly and Function Chromosome-Mediated Spindle Assembly Mitotic Chromosomes Promote Bipolar Spindle Assembly Mitotic Chromosomes Promote Bipolar Spindle Assembly Mitotic Chromosomes Promote Bipolar Spindle Assembly Metaphase Mitosis - Metaphase Kinetochores Attach Sister Chromatids to the Spindle The Ndc80 complex allows both microtubule attachment and dynamics Kinetochores Attach Sister Chromatids to the Spindle Bi-orientation Is Achieved by Trial and Error Bi-orientation Is Achieved by Trial and Error Anaphase Mitosis - Anaphase The APC/C Triggers Sister-Chromatid Separation and the Completion of Mitosis The APC/C Triggers Sister-Chromatid Separation and the Completion of Mitosis Chromosomes Segregate in Anaphase A and B Telophase Mitosis - Telophase Cytokinesis Mitosis - Cytokinesis Cytokinesis Begins with Formation of a Cleavage Furrow Actin and Myosin II in the Contractile Ring Generate the Force for Cytokinesis Actin and Myosin II in the Contractile Ring Generate the Force for Cytokinesis Endomitosis - Mitosis without Cytokinesis Mitosis Can Occur Without Cytokinesis Mitosis Can Occur Without Cytokinesis When Things Go Wrong Abnormal Cell Division Often Leads to Cancer Cell Cycle Checkpoints The Cell-Cycle Control System Functions as a Network of Biochemical Switches DNA Damage Checkpoint DNA Damage Blocks Cell Division: The DNA Damage Response Spindle Assembly Checkpoint (SAC) Unattached Chromosomes Block Sister-Chromatid Separation: The Spindle Assembly Checkpoint
Mad2 (SAC protein, inhibits APC/C) Spindle Assembly Checkpoint Quiz That’s why it’s called the “cell phone” That’s why it’s called the “cell phone”
iPhone 11/12 Cancer?