CANCER Erlix R Purnama, M.Si. Lab Fisiologi Jurusan Biologi CELL CYCLE
The eukaryotic cell
cycle usually occurs in four phases CELL-CYCLE CONTROL SYSTEM • The cell-cycle control system governs the cell-cycle machinery by complexes that initiate or regulate DNA replication, mitosis, and cytokinesis. • The phosphorylation reactions that control the cell cycle are carried out by a specific set of protein kinases, while dephosphorylation is performed by a set of protein phosphatases CELL-CYCLE CONTROL • Progression through the cell SYSTEM cycle depends on cyclin- dependent protein kinases (Cdks) • The accumulation of cyclin, helps regulate the activity of Cdks CELL-CYCLE CONTROL SYSTEM 1. G1/S-cyclins activate Cdks in late G1 and thereby help trigger progression through Start, resulting in a commitment to cell-cycle entry. Their levels fall in S phase. 2. S-cyclins bind Cdks soon after progression through Start and help stimulate chromosome duplication. S- cyclin levels remain elevated until mitosis, and these cyclins also contribute to the control of some early mitotic events. 3. M-cyclins activate Cdks that stimulate entry into mitosis at the G2/M transition. M-cyclin levels fall in mid-mitosis. • The cell-cycle control system uses various mechanisms to pause the cycle at specific transition points. • One way in which mitogens stimulate cell proliferation is by inhibiting the Rb protein. • DNA damage can arrest the cell cycle in G1 • The initiation of DNA replication takes place in two steps • Incomplete Replication Can Arrest the Cell Cycle in G2 Interphase M Phase: A. Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase B. Cytokinesis Interphase Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase A. A fluorescence micrograph of a metaphase chromosome stained with a DNA-binding fluorescent dye and with human autoantibodies that react with specific kinetochore proteins (red) B. Showing its two sister chromatids attached to the plus ends of kinetochore microtubules C. Electron micrograph of an anaphase chromatid with microtubules attached to its kinetochore MICROTUBULE ATTACHMENT SITES IN THE KINETOCHORE • Each microtubule is attached to the kinetochore by interactions with multiple copies of the Ndc80 complex (blue).
• This complex binds to the
sides of the microtubule near its plus end, allowing polymerization and depolymerization to occur while the microtubule remains attached to the kinetochore MICROTUBULE ATTACHMENT SITES IN THE KINETOCHORE Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Mitosis: 1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase Cytokinesis Mitosis: 1. Prophase