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1 Mitosis and the Cell Cycle 10/21/05. 2 Lecture Outline Two goals of the Cell Cycle: –Make one cell into two –Must accurately replicate the genetic material.

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Presentation on theme: "1 Mitosis and the Cell Cycle 10/21/05. 2 Lecture Outline Two goals of the Cell Cycle: –Make one cell into two –Must accurately replicate the genetic material."— Presentation transcript:

1 1 Mitosis and the Cell Cycle 10/21/05

2 2 Lecture Outline Two goals of the Cell Cycle: –Make one cell into two –Must accurately replicate the genetic material Mitosis (replicate and distribute the chromosomes) –Major phases –Mechanics of chromosome segregation Cytokinesis (how does one cell become two?) Replication of the cytoplasm and organelles Control of the Cell Cycle –Cyclins and CDKs –The importance of checkpoints for quality control

3 3 Phases of the Cell Cycle The cell cycle consists of –The mitotic phase (M) –Interphase G1 S G2 INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5

4 4 Mitosis and the Cell Cycle Genetic information is copied exactly into each daughter cell See it in action

5 5 Each duplicated chromosome Has two sister chromatids, which separate during cell division 0.5 µm Centromere Sister chromatids Centromeres Sister chromatids Figure 12.4 One chromosome, one DNA molecule Duplication One chromosome, two DNA molecules (Two attached chromatids) Sister chromosomes separate during mitosis

6 6 G 2 OF INTERPHASE PROPHASE PROMETAPHASE Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Kinetochore Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore microtubule Figure 12.6 Nonkinetochore microtubules Overview of Mitosis DNA replication during Interphase Prophase: Chromosomes begin to condense. Spindle starts to form Prometaphase: Nuclear envelope breaks down. Chromosomes attach to spindle

7 7 Centrosome at one spindle pole Daughter chromosomes METAPHASEANAPHASETELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Figure 12.6 Overview of Mitosis Metaphase: Chromosomes align in center of cell Anaphase: Sister chromatids separate Telophase: Complete set of chromosom es at each pole

8 8 Balanced attachment of spindle fibers to both chromatids aligns chromosomes in metaphase “tug of war”

9 9 CentrosomeAster Sister chromatids Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules Centrosome Chromosomes Microtubules 0.5 µm 1 µm Figure 12.7 Nonkinetechore microtubules from opposite poles overlap and push against each other, elongating the cell Kinetochore microtubules attach to centromeres and direct the poleward movement of chromosomes Both chromatids must be captured by spindle fibers. If any kinetochores remain unattached, chromosomes will not separate

10 10 Mark Spindle fibers shorten at the kinetochore

11 11 Kinetochore Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin subunits

12 12 Cytokinesis Animal cells divide by c on s t ri c ti o n Cleavage furrow Contractile ring of microfilaments Daughter cells 100 µm (a) Cleavage of an animal cell (SEM) Figure 12.9 A Daughter cells 1 µm Vesicles forming cell plate Wall of patent cell Cell plate New cell wall (b) Cell plate formation in a plant cell (SEM) Figure 12.9 B Plant cells build a partition (cell plate)

13 13 How do the cytoplasmic organelles divide? Mitochondria (and chloroplasts) are present in multiple copies, and randomly segregate into the two daughter cells. Membrane bound organelles (e.g. ER) fragment along with the nuclear membrane and are reconstructed in the daughter cells

14 14 Phases of the Cell Cycle The cell cycle consists of –The mitotic phase (M) –Interphase G1 S G2 INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5

15 15 The clock has specific checkpoints: the cell cycle stops until a go-ahead signal is received G 1 checkpoint G1G1 G1G1 G0G0 (a) If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. (b) If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state. Figure A, B See cell-cycle game at:

16 16 Cell Cycle Control System Figure Control system G 1 checkpoint G1G1 S G2G2 M MITOSIS EXIT: –All chromosomes attached to spindles? S-PHASE ENTRY (G1/S) –Mitosis Complete? –Growth/ Protein Synthesis adequate? –No DNA Damage? MITOSIS ENTRY (G2/M) –Replication Complete? –Growth/ Protein Synthesis adequate? –No DNA Damage?

17 17 The Cell Cycle Clock: Cyclins and Cyclin-dependent kinases Cyclins –G1 cyclin (cyclin D) –S-phase cyclins (cyclins E and A) –M-phase cyclins (cyclins B and A) Cyclin-dependent kinases (Cdks) –G1 Cdk (Cdk4) –S-phase Cdk ((Cdk2) –M-phase Cdk (Cdk1) Cyclin levels in the cell rise and fall with the stages of the cell cycle. Cdk levels remain stable, but each must bind the appropriate cyclin (whose levels fluctuate) in order to be activated.

18 18 Phosphorylation of CDK Targets Changes Their Activity Now performs a cell cycle function

19 19 The Human Cell Cycle ~ 10 hours ~ 9 hours ~ 4 hours ~ 1 hour

20 20 How does the cell cycle cycle? Focus first on entry and exit from mitosis

21 21 MPF triggers: –assembly of the mitotic spindle –breakdown of the nuclear envelope –condensation of the chromosomes Cyclin component degraded in anaphase Cyclin B synthesized in S phase; Combines with cdk1 to make active MPF Cyclin-CDK controls the cell cycle

22 22 Cyiclin-CDK activity can also be controlled by inhibitors The Cell Cycle According to Cyclin Abundance

23 23 How are CDKs Regulated? Isolate mutants that divide too early or too late

24 24 CDKs are Regulated by Phosphorylation is a kinase is a phosphatase CAK (CDK Activating Kinase)

25 25 Conformational Changes Associated with CDK Phosphorylation The T-loop blocks substrate access Free CDKCDK + CyclinT161 phosphorylation Binding of cyclin moves the T-loop Phosporylation moves the T-loop more

26 26 Cyclin Dependent Kinase Inhibitors (CKIs) Cyclin CDK p21 Cyclin CDK4 Cyclin CDK CDK4 p16 p21

27 27 Cell Cycle Regulators and Cancer

28 28 Triggers: Chromosome separation Breakdown of cyclin to re-start the cycle Breakdown of geminin (to again allow replication) Anaphase promoting complex


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