D103 - Lecture 24 - Mitosis.docx

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Biological Sciences
Grant Mac Gregor

A. Office Hour a. Kinesin 13 i. Catastrophe factor b. XMAP215 i. Stabilizing MAP b. JAK kinase i. Cross-talk ii. Can also be Involved in RTK signaling 1. Ras/MAP Kinase 2. PI3 Kinase 3. PLC/DAG/PKC A. Mitosis a. Facts i. No protein synthesis during mitosis ii. Centrosomes separate sister chromatids iii. Microtubule spindle forms to separate chromosomes B. Centrosomes a. Duplicate during interphase b. Mother centriole is older than the daughter B. Cohesins a. Mediates cohesions between sister chromatids b. Phosphorylation on cohesins on chromosome arms causes dissociation i. Prior to metaphase b. During Metaphase i. Cohesins are only present on the centromere area B. Condensins a. Requires ATP for chromosome condensation i. Possible without condensins, but chromosomes become fragile b. Phosphorylation i. By M-CDK ii. Triggers assembly on chromosome B. Microtubule Dynamic Instability a. Stathmin i. Microtubule binding protein 1. Reduces the local concentration of free dimeric tubulin 2. MT gets unstable b. MAP i. Microtubule associated proteins ii. Kinesin-13 1. Catastrophin 2. Decrease the stability b. Elongates twice as fast during mitosis i. Shortens at the same rate b. Interphase MT - can recover c. Mitosis MT - cant recover i. MT lengths are shorter during mitosis ii. More unstable B. XMAP215 a. Stabilizing MAP b. Phosphorylated by M-CDK before mitosis B. Kinesin-13 a. Destabilizing MAP b. Catastrophin B. Mitotic Spindle a. Microtubules i. Astral 1. Project from the poles 2. Orients the spindle ii. Interpolar 1. Minus end is near the centrosomes 2. Plus end is near the zone of inter-digitation ii. Kinetochore 1. Plus ends are embedded in the kinetochore 2. Minus ends are near the spindle pole B. Motor Proteins a. Kinesin i. 4, 10 1. Plus-end 2. Binds to chromosomes 3. Moves them to the plus end of the kinetochore MT 4. One motor domain ii. 5 1. Plus-end 2. 2 motor domains 3. Binds to interpolar MT a. Pushes them apart b. Helps in anaphase B ii. 13 1. catastrophin 2. No motor activity 3. Mediates disassembly at the + end of the kinetochore MT ii. 14 1. Minus end 2. Single motor domain 3. Binds to interpolar? MT and pulls them together 4. Inactivation leads to anaphase B b. Dynein i. Minus end ii. Single motor domain iii. Cell cortex as cargo, and pulls toward the minus end of the centrosome iv. Tension v. Helps in anaphase B B. Chromosome Capture a. Kinetochore MT b. 'search' and capture mechanism c. One centrosome attached to opposite kinetochores makes the most stable outcome d. Tension i. Increases affinity for MT for kinetochore B. Kinetochore a. Fibrous Corona i.
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