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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