320_23&24 - Cel l cycl e, cancer & devel opment...

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22-23 Becoming multicellular - cell division, the cell cycle and cancer 23-24 Differentiation and patterning. - early development in Drosophila Text Question bank D #40 - 101
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Cell division, the cell cycle and cancer Regulating cell division the cell division cycle Cancer as a defect in cell proliferation tumorigenesis oncogenes tumor suppressors Reading: textbook, chapter 19. Ridley, chapter 17.
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Cells are complex Many events and processes must occur for successful cell division: cell growth nuclear envelope breakdown spindle assembly centrosome duplication DNA replication chromatin condensation chromosome segregation
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Cells are complex Many events and processes must be coordinated for successful cell division: DNA replication nuclear envelope breakdown spindle assembly chromatin condensation cell growth centrosome duplication chromosome segregation
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Phases of the cell cycle growth G2 G1 growth DNA replication S M mitosis interphase mitotic index: % of cells in mitosis - a measure of proliferation & centrosome
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Some cell cycles are shorter: S M G2 S M Drosophila embryo development: cycles 1-13 (20 min each) cycles 14-16+ The cycle stops as cells differentiate G2 G1 S M G0
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The cell cycle is driven by a biochemical “clock”… G2 G1 S M ..and can also be regulated by outside signals.
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The cell cycle in budding yeast cells synchronized by adding mating factor
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Gene expression in the cell cycle (different methods for synchronizing cell cycles) Histone genes Clicker question - needed In which phase? A. G1 B. S C. G2 D. M
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Finding cell division cycle (CDC) mutants Screen for conditional lethal mutations in yeast: budding yeast cell-lethal mutant Different CDC mutants arrest at different phases of the cycle cell-cycle mutant shift to 36 o C
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Finding cell division cycle (CDC) mutants permissive temperature restrictive temperature (text fig 18.4)
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Cell division cycle ( cdc ) mutations specifically identify genes whose normal protein products… A) … are temperature-sensitive. B) … are required throughout the cell cycle. C) … are required at a particular phase of the cell cycle. D) … are expressed throughout the cell cycle. E) … are expressed at a particular phase of the cell cycle. Clicker question G2 G1 S M cdc2 ts CDC2 encodes DNA polymerase III. cdc2 null mutants are always lethal.
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Some CDC mutants affect proteins that regulate the cell cycle CDC28 encodes a cyclin-dependent protein kinase (CDK) C D K   ( i n a c t i v e ) C y c l i n C y c l i n - C D K c o m p l e x P S u b s t r a t e p r o t e i n
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Cyclins regulate cyclin-dependent kinases Cyclin levels rise and fall at different phases of the cell cycle G1 S G2 M G1 S G2 M M CyclinD CyclinA Cyclin D - CDK4 active in G1 inactive in S, G2 P R b E 2 F R b E 2 F transcription factor S phase genes transcribed Cyclin D destroyed (proteases) Cyclin A synthesized
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Cell cycle checkpoints - ensure one stage is completed before the next is begun
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320_23&24 - Cel l cycl e, cancer & devel opment...

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