Ch. 12 The Cell Cycle

1. INTERPHASE S(DNA synthesis) G1 CytokinesisMitosis G2 MITOTIC(M) PHASE Ch. 12 The Cell Cycle • Interphase • M phase • Mitosis • Cytokinesis

2. Cell Division - Purpose 100 µm 200 µm 20 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). (b) Growth and development. This micrograph shows a sand dollar embryo shortly after the fertilized egg divided, forming two cells (LM). (c) Tissue renewal. These dividing bone marrow cells (arrow) will give rise to new blood cells (LM). • Reproduction – unicellular organisms – binary fission in bacteria • Growth & development from fertilized egg • Repair (& replacement) of damaged cells

3. A eukaryotic cell has multiplechromosomes, one of which is represented here. Before duplication, each chromosomehas a single DNA molecule. Once duplicated, a chromosomeconsists of two sister chromatidsconnected at the centromere. Eachchromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. Figure 12.4 Chromosome duplication and distribution during cell division 0.5 µm Chromosomeduplication(including DNA synthesis) Centromere Sisterchromatids Separation of sister chromatids Centrometers Sister chromatids

4. INTERPHASE S(DNA synthesis) G1 CytokinesisMitosis G2 MITOTIC(M) PHASE Figure 12.5 The cell cycle 90% of cell’s life 5-6hrs. 10-12hrs. growth growth 4-6hrs. 1hr.

5. INTERPHASE S(DNA synthesis) G1 G2 CytokinesisMitosis MITOTIC(M) PHASE An organism’s genome: • Total genes in the cell of a species • Nuclear & extra-nuclear (mito & chloro) Human chromosome number: • 46 – somatic cell (body cells) • 2n • diploid • 23 – gamete (sex cells – sperm & egg) • n • haploid Chromosomes: • Chromatin • DNA & proteins

6. Interphase Centromsomes – with 2 centrioles Nucleus – with mass of chromatin Nucleolus in nucleus

7. INTERPHASE S(DNA synthesis) G1 G2 CytokinesisMitosis MITOTIC(M) PHASE Phases of Mitosis • Prophase Prometaphase – chromosomes are in Pairs • Metaphase – chromosomes in Middle • Anaphase – chromosomes Apart • Telophase – Two cells

8. PROMETAPHASE G2 OF INTERPHASE PROPHASE Centrosomes(with centriole pairs) Aster Fragmentsof nuclearenvelope Early mitoticspindle Kinetochore Chromatin(duplicated) Centromere Kinetochore microtubule Chromosome, consistingof two sister chromatids Nuclearenvelope Plasmamembrane Nucleolus Figure 12.6 Exploring The Mitotic Division of an Animal Cell Nonkinetochoremicrotubules

9. METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS Metaphaseplate Cleavagefurrow Nucleolusforming Nuclear envelopeforming Spindle Figure 12.6 Exploring The Mitotic Division of an Animal Cell Daughter chromosomes Centrosome at one spindle pole

10. Cytokinesis: • division of the cytoplasm • animal cells • Forms cleavage furrow • plant cells • Forms a cell plate

11. 100 µm Cleavage furrow Vesiclesforming cell plate 1 µm Wall of patent cell Cell plate New cell wall Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM) Figure 12.9 Cytokinesis in animal and plant cells Daughter cells

12. G1 checkpoint Control system S G1 G2 M G2 checkpoint – cyclin dependent complex CDK complex (go ahead signal) M checkpoint Molecular Control of Cell Cycle • regulated at checkpoints • kinases - cyclin-dependent kinase (CDK) • cyclins • MPF • maturation promoting factor • Cyclin + CDK = MPF • (mitosis promoting factor)

13. G0 G1 checkpoint G1 G1 (b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. (a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues      on in the cell cycle. Figure 12.15 The G1 checkpoint

14. 3 MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. (breaking down nuclear envelop, etc.) Figure 12.16 Molecular control of the cell cycle at the G2 checkpoint G1 G1 M G2 G2 (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle S S M MPF – maturation promoting factor MPF activity Cyclin Relative Concentration Time (b) Molecular mechanisms that help regulate the cell cycle 1 Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates. 5 During G1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. G1 S Cdk M G2 DegradedCyclin G2checkpoint 2 Accumulated cyclin molecules combine with recycled Cdk mol- ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis. Cdk Cyclin is degraded Cyclin MPF 4 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase.

15. Control of Cell Cycle • Cyclin accumulates - late S phase • Binds to/activating CDK • Producing MPF • MPF at G2 initiates mitosis • Anaphase - cyclin component of MPF degrades • M phase terminates - cell -> G1

16. CONCLUSION This experiment demonstrated that during anaphase, kinetochore microtubules shorten at their kinetochore ends, not at their spindle pole ends. This is just one of the experiments supporting the hypothesis that during anaphase, a chromosome tracks along a microtubule as the microtubule depolymerizes at its kinetochore end, releasing tubulin subunits Chromosomemovement Kinetochore Tubulinsubunits Microtubule Motorprotein Chromosome Kinetochore microtubules shorten at their kinetochore ends

17. Prophase: • chromatin - condenses • nucleoli disappear. • sister chromatids appear • mitotic spindle forms • centrosomes move away from each other

18. Prometaphase: • nuclear envelope fragments • microtubules join chromosomes • 2 chromatids/chromosome • kinetochore center • “kinetochore microtubules.” - jerk the chromosomes back and forth. • Nonkinetochore microtubules interact with opposite poles

19. Metaphase: • Metaphase - longest stage • about 20 min. • centrosomes at opposite ends. • chromosomes convene on metaphase plate, • at centromeres • Sister chromatid kinetochores • attached to kinetochore microtubules • spindle - apparatus of microtubules

20. Anaphase: • shortest stage - a few minutes. • 2 sister chromatids part • chromatid becomes chromosome • move toward opposite ends of the cell, • kinetochore microtubules shorten • cell elongates • nonkinetochore microtubules lengthen • finally the ends have equivalent—complete— collections of chromosomes

21. Telophase: • 2 daughter nuclei form • Nuclear envelopes form • chromosomes -less condensed • Mitosis • the division of 1 nucleus into 2 genetically identical nuclei - complete

22. Aster Centrosome MetaphasePlate Sisterchromatids Kinetochores Overlappingnonkinetochoremicrotubules Kinetochores microtubules 0.5 µm Microtubules Chromosomes Centrosome 1 µm Figure 12.7 The mitotic spindle at metaphase

23. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. (a) If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Cancer cells do not exhibitanchorage dependence or density-dependent inhibition. Cancer cells. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. (b) 25 µm Lack of Cell Cyle Controls - Cancer Cells Figure 12.18 Density-dependent inhibition and anchorage dependence of cell division

24. 2 4 3 1 Lymphvessel Tumor Bloodvessel Glandular tissue Cancer cell MetastaticTumor A small percentage of cancer cells may survive and establish a new tumor in another part of the body. A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. Figure 12.19 The growth and metastasis of a malignant breast tumor

25. 1 2 3 4 5 Chromatinecondensing Nucleus Chromosome Nucleolus Metaphase. The spindle is complete,and the chromosomes,attached to microtubulesat their kinetochores, are all at the metaphase plate. Prometaphase.We now see discretechromosomes; each consists of two identical sister chromatids. Laterin prometaphase, the nuclear envelop will fragment. Telophase. Daughternuclei are forming. Meanwhile, cytokinesishas started: The cellplate, which will divided the cytoplasm in two, is growing toward the perimeterof the parent cell. Prophase. The chromatinis condensing. The nucleolus is beginning to disappear.Although not yet visible in the micrograph, the mitotic spindle is staring to from. Anaphase. Thechromatids of each chromosome have separated, and the daughter chromosomesare moving to the ends of cell as their kinetochoremicrotubles shorten. Lab: Figure 12.10 Mitosis in a plant cell

26. Plant Cells – meristematic tissue (root tip)

27. Origin of replication 4 3 1 2 Cell wall Plasma Membrane E. coli cell Bacterial Chromosome Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy ofthe origin is now at each end of the cell. Origin Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result. Bacterial cell division (binary fission)