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Transcript
Cell Cycle Regulation Kinetochore Today s topics: • Mitosis – How do chromosomes line up? – How do chromosomes separate? – How do cells divide? Chromosome movement • Cell cycle checkpoints Kinetochore – Cyclins – Cyclin-dependent kinases • Apoptosis • Cancer Microtubule Tubulin subunits Motor protein Chromosome Oct 24, 2016 2 1 Cytokinesis Spindle fibers shorten at the kinetochore Animal cells divide by constriction Mark Cleavage furrow 100 µm Plant cells build a partition Vesicles forming cell plate 1 µm Contractile ring of microfilaments 3 4 The cell cycle is tightly controlled How do the cytoplasmic organelles divide? • MITOSIS ENTRY (G2/M) – Replication Complete? – Growth/ Protein Synthesis adequate? – No DNA Damage? • Mitochondria (and chloroplasts) are present in multiple copies, and randomly segregate into the two daughter cells. • The ER and Golgi fragment along with the nuclear membrane and are reconstructed in the daughter cells 5 • MITOSIS EXIT: – All chromosomes attached to spindles? • S-PHASE ENTRY (G1/S) – Mitosis Complete? – Growth/ Protein Synthesis adequate? – No DNA Damage? 1 Cyclins and CDKs The Human Cell Cycle ~ 1 hour ~ 4 hours ~ 10 hours ~ 9 hours 7 Phosphorylation of CDK Targets Changes Their Activity Now performs a cell cycle function 9 CDK is present, Figure but inactive 7.10 CyclinsCyclin Are synthesized in Transient in the Cell Cycle G1 How does the cell cycle cycle? Focus on G1àS Restriction point Growth factor signal 10 Here is a figure from Chapter 5. Can you explain what is happening? Figure 5.13 A Protein Kinase Receptor Now CDK is active Cyclin breaks down when no longer needed Think about: reception, transduction, response. How does it work? 2 E2F is a transcription activator Growth factor Reception à Signaling cascade à à Production of cyclin Now CDK active E2F Released S phase genes transcribed Nature Reviews Urology 9, 41-51 Rb represses E2F Cyclin/Cdk inactivates Rb by phosphorylation. Releases E2F Now the Sphase enzymes are made 13 Various kinds of Cyclin-CDK Inhibitors Apoptosis: Programmed Cell Death p21 CDK CDK Cyclin Cyclin p21 p16 CDK4 Cyclin CDK4 p16 15 Cell Cycle and Cancer What is the connection? Cell Cycle Regulators and Cancer 18 3 HPV and Cancer Growth factor Signaling cascade à à Production of cyclin Reception à Now CDK active E2F Released Nature Reviews Urology 9, 41-51 HPV virus does two things: 1) blocks Rb How could that lead to cancer? Many changes are needed for a cell to become cancerous S phase genes transcribed 20 HPV virus does two things: 2) blocks p53 and p21 How could that lead to cancer? Cancer risk increases with age It takes many years for the causative mutations to accumulate in a cell lineage 4
