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Mitotic Cell Cycle
DNA
Replication
G1
S
G2
M-Phase
G1
Binding site for
Origin Recognition Complex (ORC)
(ORC)
Semi-Conservative DNA Replication
(G1 Phase)
(G2 Phase)
Completing Synthesis of the Lagging Strand
*
(5’ to 3” exonuclease)
*
DNA Polymerase “proof reading”
Thymine Tautomers
(common form)
Pairs with Adenine
(rare form)
Pairs with Guanine
End Replication Problem
A
First round of
DNA replication
*
*
*
*
Final RNA primers
removed
Second round of
DNA replication
Telomere Synthesis
Telomere Synthesis
Normal Cell Telomeres
Short Telomeres
Apoptosis
Telomerase Inhibitor
Telomostatin
Apoptosis
Cohesion of Sister Chromatids
Interphase and M-Phase Chromosomes
Condensation of Chromatids
Kinetochore
Pg. 645
Kinetochore
Mitotic Spindle
Mitotic Spindle
Metaphase
Pg. 641
Anaphase
Start of Anaphase
P
Anaphase “A” and “B”
Nuclear Lamina
Pg. 576
Control Points in the Mitotic Cell Cycle
Positive Control by
Cyclin/Cdk
Negative Control
By p53
Cyclin Protein Levels Vary
During the Cell Cycle
Ubiquitin-dependent Protein Degradation
Protein
+
Ub
APC (Ubiquitin Ligase)
Protein
Ub-Ub-Ub
Proteasome
Pg. 257
Peptides + Ub
Cyclin/Cdk Complexes During the Cell Cycle
Expression of
M-cyclin Gene
Ubiquitin-dependent
proteolysis
Ubiquitin-dependent
proteolysis
Expression of
S-cyclin Gene
Cyclin/Cdk Phosphorylates Rb Protein
(RTK)
(Ras-MAP Kinase)
Activation of
“S-Phase Genes”
Inactivating the Cyclin/Cdk Complex
Active Cdc4 Ubiqutin Ligase
Cyclin/Cdk Complexes During the Cell Cycle
Expression of
M-cyclin Gene
Ubiquitin-dependent
proteolysis
Ubiquitin-dependent
proteolysis
Expression of
S-cyclin Gene
Cell Cycle Checkpoints
The p53 Cell Cycle Checkpoint
or Short Telomeres
DNA Repair System
Apoptosis
Cyclin/Cdk Complexes During the Cell Cycle
Expression of
M-cyclin Gene
Ubiquitin-dependent
proteolysis
Ubiquitin-dependent
proteolysis
Expression of
S-cyclin Gene
Cyclin/Cdk Phosphorylates Nuclear Lamins
M-Cyclin/Cdk
Cyclin/Cdk Phosphorylates APC
P
M-Cyclin/Cdk
Normal
Cell
Apoptotic
Cell
The “Death” Receptor
Release of Cytochrome C
from Mitochondria
Pg. 628
Caspase Activation
Pg. 627
Caspase Cascade
Pg. 627
Overview of Mammalian Development
(~ 9 weeks)
Asymmetric Cell Divisions of Meiosis
(Metaphase II)
(Mitosis)
Egg Cell and Sperm Cells
Pg. 661
“Cleavage” Divisions
50 µm
8 cell Embryo (morula)
Blastocycst
Uterus
Inner Cell Mass
(ICM)
Blastocyst
Blastocoel
Trophoblast
50 µm
Early Embryonic Development (~ 7 days)
Drosophila melanogaster (a.k.a. Fruit Fly)
The eyeless (ey) Gene Controls Eye Development
Ectopic Expression
of ey Gene
Pg. 288
Expression of ey Gene
in Leg Precursor Cells
Ectopic Expression
of Mouse ey Gene
Group of cells
that give rise to
adult wing
Pg. 288
Expression of Mouse ey Gene
in Wing Precursor Cells
Homeotic Genes
Synpolydactyl Phenotype
HoxD13 mutation
Stem Cell Concept
Signal Molecules?
Pg. 721
Pluripotent Embryonic Stem Cells
Signal A
Signal B
Signal C
IVF
“Stem Cell Line”
Signal D
Signal E
Pg. 724
Colony of Embryonic Stem Cells
Teratomas
Neural
epithelia
Bone
Retinal
epithelia
Cartilage
Somatic Cell Nuclear Transfer
“Donor”
Reconstructed
Zygote
“enucleated egg”
Pg. 725
Somatic Cell Nuclear Transfer
“Donor”
Reconstructed
Zygote
“enucleated egg”
Pg. 725
Pluripotent Stem Cells
Without Embryos?
November 20, 2007
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