cell cycle
TRANSCRIPT
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The cell cycleprokaryoticeukaryotic
Control of the cell cycleloss of control- cancer
What is cell differentiation and why does it happen?what is a stem cell?
What is cloning?implications of cloning
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Cell divisionprokaryotes- binary fission
one bacterium divides into twoone circular chromosome replicates
beforehandtwo identical daughter cells formcan take as little as 15 minutes
eukaryotesDNA is replicated before cell divisionsomatic cells- mitosis
two identical daughter cellsgerm cells- meiosis
gametes (sperm and eggs) whichfuse to form a zygotetakes much longer
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Eukaryotic cells have several chromosomes
Number varies among species (p. 138)humans have 46 (23 pairs)
diploid organisms have pairs ofchromosomes
chromosome structure is complex
How much of that chromosome actually containsgenetic information?
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How long does the cell cycle last?
Depends on the cellstem cells, embryonic cells- a few hours(embryonic cells don’t really have G1 andG2- why?)
Some cells divide very slowly
Some cells divide when inducedliverlymphocytes
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Cell division
Cells grow during interphaseDNA is replicated during S phase
Division of nucleus during M phase (mitosis)Division of cytoplasm (cytokinesis)
Programmed cell death (apoptosis)
Cells divide only a certain number of timesand then die (Hayflick limit)
Role of telomeres?
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Control of cell cycle- by special proteins andenzymes that act as switches
G1 checkpoint- stop, pause or go into S phasesome cells stop permanently
G2 checkpoint- will cell divide?
M checkpoint- formation of new cells
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M phase drives G1 cell into mitosis, even thoughS phase has not occurred
S + G1: G1 cell starts S phaseS phase + G2: G2 will not undergo DNA synthesis
Early 1970s
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I. G1 varies the most among cell typesfirst of several checkpoints is seen
What determines whether a cell will grow?
Single-celled organisms grow if enough nutrientsare present
Multicellular organisms must grow in a controlledway: growth factors
Mitogens stimulate cells to go into S phase
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Many growth factors have been describedhow do they work?
Bind to tyrosine kinase receptorsActivate Ras pathway (a small membrane G
protein)↓
Cascade of phosphorylation reactions, followedby transcription
Cell passes into S phase
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II. G2 checkpoint (between G2 and M)
DNA synthesis must be complete and correct
Cell may be arrested at this point
This checkpoint tends to be more importantin certain types of cells, e.g., fertilizedfrog eggs and certain strains of yeast
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Cyclin-dependent kinases (Cdk)first discovered in yeast
Different kinds of cyclins; levels oscillate at different stages of cycle
Control mechanismsavailability of cyclins variesCdk must be phosphorylated
Cyclin and Cdk must be bound together to beactive
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Initial cyclin-Cdk complex is inactivea series of phosphorylation and dephos-phorylation steps make it active
Complex is called MPF (mitosis-promotingfactor)
Present in both mitosis and meiosishighly conserved
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MPF activates acomplex thatdegrades cyclin
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G1 checkpoints
Rb prevents cell moving into S phase by bindingto a transcription factor
When Rb is phoshporylated it cannot bind socell can move into S phase
p53 prevents damaged from dividing (by inhibitingRb pathway)
Abnormalities in both genes are associated withhereditary forms of cancer
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III. Spindle assembly checkpoint, betweenmetaphase and anaphase
Cell cycle can be arrested if spindle fibers arenot attached properly to chromatids
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Cell growth is usually tightly regulated
Controls:contact inhibition- cells will grow to a
certain density
finite number of cell divisions
“gatekeeper genes”proto-oncogenes- stimulate growth
some make growth factorssome respond to growth factors
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Types of proto-oncogenes
Growth factorsReceptors (G protein and tyrosine kinase)KinasesTranscription factorsCdk-kinases
Mutant forms, oncogenes that promote cancer,have been identified in every category
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Tumor suppressors- inhibit cell growth
Cancers occur when cells grow out of control
invade and damage tissues
cells themselves may not functionproperly
How does this happen? Mutations accumulatein DNA
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If mutations occur in control genes, they can’tregulate cell growth
Some defects in particular genes are associatedwith specific cancers
BRCA-1 tumor suppressor gene associated withsome inherited breast cancers
p53- tumor suppressor- associated with manycolon, bladder, breast, brain, lung cancers(about half of all cancers!)
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What about this “cell destruction”?
Damaged cell undergoes apoptosis(programmed cell death)
Genetically regulated- cell has genes that bothpromote and inhibit death
How does programmed cell death differ fromdeath by injury?
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Inheritance of “cancer gene”:
Each cell has 2 copies of p53. If both becomedamaged, they lose control of cell growth
If you inherit one “damaged” copy, you’re halfway there!
Mutations occur over time- cancer is more common in older people
Most cancer is NOT inherited; environmentaldamage causes most cancer
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What sorts of things cause this damage?
Radiation
Toxins
Chemicals
Our bodies have many processes that repairdamaged DNA
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Avoid sun exposure
Avoid smoking
Eat moderately; consume fiber. Some foodsmay help prevent cancer?
Early detection (especially important if youhave a family history of cancer)
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As more is known about mechanisms ofuncontrolled cell growth, new treatmentstrategies will emerge
RadiationChemotherapyImmunotherapyKinase inhibitorsAngiogenesis inhibitorsGene replacement