Cell Cycle

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Cell Cycle

• Stages cells pass through from 1 cell division to
  the next

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In order for cell to divide, 4 events must occur

• Reproductive signal
• DNA replication
• Segregation of chromosomes
• Cytokinesis

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Comparing Pro- and Eukaryotes

• Prokaryotes
• Cell division reproduction of the organism
• Reproductive signal usu. triggered by external
  factors
• Eukaryotes
• Cell division can reproduction of organism
• Multicellular eukaryotes also use for growth and
  repair of tissue
• Signals for division relate to needs of entire
  organism

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2 Main Phases of Cell Cycle

• Interphase
• Active metabolism
• Synthesizes needed materials
• No cell division
• M phase
• Mitosis
• cytokinesis

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Interphase has 3 key stages

• G1 phase
• Growth
• Normal metabolism
• Cells that are not dividing become arrested here
  and enter G0
• S phase
• DNA replication
• Synthesis of histones
• G2 phase
• Final prep for division (protein synthesis)

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Internal Control of Cell Cycle

• Under optimal conditions, length of eukaryotic
  cell cycle is constant for given cell type
• Regulatory molecules control cell cycle
• Genetically programmed in nucleus
• Trigger specific events

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Cell Cycle Checkpoints

• Control Cell Division
• Genetically programmed to ensure that the events
  of one stage of cell cycle is complete before
  next begins

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Cell Cycle Checkpoints

• 1st most important restriction point
• Late in G1
• Ensures cell is large enough
• G2-M checkpoint makes sure replication is
  complete
• Metaphase checkpoint chromosomes properly
  attached to spindle
• http//www.cellsalive.com/cell_cycle.htm
• http//nobelprize.org/educational_games/medicine/2
  001/cellcycle.html

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Regulation of Cell Cycle

• Length of cell cycle varies with organisms and
  type of cells
• Regulatory molecules in eukaryotes control cell
  cycle
• Cyclin-dependent kinases (CDKs) activate or
  deactivate other proteins by phosphorylating them
• Cyclins
• Regulatory proteins
• Bind to Cdks to turn them on
• Levels fluctuate predictably during cell cycle

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Regulation, cont.

• Specific cyclin binds to specific CDK, forming
  cyclin-CDK complex
• Turns enzymes on/off by phosphorylating them
• Ex. p27
• Protein that inhibits cell division
• When phosphorylated p27 degrades and cell can
  divide

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4 Major Cyclin-CDK Complexes

• G1-CDK prepares cell to pass from G1 to S phase
• G1/S-CDK commits the cell to replication
• S-CDK initiates replication
• M-CDK
• Promotes mitosis
• Activates APC

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External Control of Cell Cycle

• Certain drugs can stop cell cycle at specific
  checkpoint
• Hormones
• Plants cytokines
• Animals steroids and protein hormones
• Density of cells
• Crowding regulates cell division

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Cancer

• Cells lack normal inhibitions
• Large of cells undergoing mitosis
• Reduced contact inhibition
• Reduced dependence on growth factors
• Apparently unlimited of generations
• Cancer cells have unique characteristics
• Nucleus makes up large portion of cell
• May lose traits of original cell
• Genetically unstable
• Duplications, deletions, rearrangements of
  chromosomes

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Cancer as a Multi-Step Process

• Altered expression of specific genes
• Normal genes mutate into cancer-causing genes
• Proto-oncogenes ? oncogenes
• Overactive growth-promoting pathways
• Tumor suppressor genes
• Block cell division

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Back-Up Systems

• DNA repair system
• Apoptosis
• Telomeres
• For cancer to develop, mutations triggering
  cancer have to occur and the bodys natural
  back-ups fail