Lecture 9: The Cell Cycle

The Cell Cycle Which cells divide? Cells divide during development Examples of the cells that divide in an adult organism: Epidermis or the skin Epithelial lining of the gut Bone marrow cells generate blood cells and immune system cells Liver cells divide when damaged Neuron cells do not divide • A. True • B. False The cell cycle Chromosome replication Chromosome segregation Cell division Mitosis is the longest stage of the cell cycle • A. True • B. False The phases of cell cycle Mammalian cell division ~24 hours G1: ~6-10 hours S: ~10-12 hours G2: ~4-5 hours M: ~0.5 hour A part of cytokinesis happens during _____ • A. M-phase • B. Mitosis • C. All of the above Control over the cell cycle Feature of cell cycle stages are different for different organisms and cells Cell cycle control is conserved in eukaryotes Cell cycle control was studies on model systems: yeast, frog embryos, cultured mammalian cells What is cell cycle control system for? Provide a certain amount of time for each event Maintain a correct order of events Each event should only occur once per cycle Complete the event Back-up systems Respond to conditions outside the cell What makes the cell go through the cell cycle? Cyclins and others Cyclins go through cycles of synthesis and degradation How do cyclins regulate the cell cycle? Cyclins bind to cyclin-dependent kinases (Cdks) Cyclin-dependent kinases activate other proteins by adding phosphate groups Cyclins also direct Cdks to certain proteins How is Cdk activated? Binding of a cyclin removes the block from the active sit of Cdk Cdk-activating kinase (CAK) further increases Cdk activity by phosphorylation Cyclin-Cdk complexes Cyclin concentration changes throughout the cycle Cdk concentration is the same throughout the cycle Cdk is only active when bound to cyclin Cyclin-Cdk complexes trigger cell cycle events Four different classes of cyclins in mammals; each present during a certain interval in the cell cycle G1-cyclins Promote passage through start G1/S-cyclins Bind Cdks at the end of G1 Commits the cell to DNA replication S-cyclins Bind Cdks during S-phase Required for the initiation of DNA replication M-cyclins Promote mitosis Fine-tuning or cyclin-cdk activity Phosphorylation at a different location has an inhibitory effect Which of the following is true? • A. Cyclin is always in an complex with cdk • B. There are both inhibitory and activating phosphates on a cdk • C. Cyclin is a kinase that phosphorylates cdk • D. None of the above CKI is ______ • A. A kinase • B. A phosphatase • C. None of the above What regulates the concentration of cyclins? Ubiquitin ligase add ubiquitin chains, which mark proteins for destruction Anaphase promoting complex (APC) is a ubiquitin ligase Proteolysis by APC happens ____ • A. By cleaving a protein by APC • B. By addition of ubiquitin chains that signal for a protein to be degraded by a proteasome Oscillation of the cell cycle Embryonic cell cycle is simple: alternating S and M Assume that cyclin M is continuously synthesized When cyclin M-Cdk reaches a certain level, it activates its own destruction protein Cdc20-APC Cdc20-APC leads to the cyclin degradation Cyclin was activating Cdc20-APC and cyclin is gone now, so the activity of Cdc20-APC drops, so nothing degrades the cyclin again Cyclin level goes up