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Ch 12 The Cell Cycle. What is the cell cycle in eukaryotes? Just as organisms have a life cycle (birth-->maturation-->reproduction->-death) Each cell.

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Presentation on theme: "Ch 12 The Cell Cycle. What is the cell cycle in eukaryotes? Just as organisms have a life cycle (birth-->maturation-->reproduction->-death) Each cell."— Presentation transcript:

1 Ch 12 The Cell Cycle

2 What is the cell cycle in eukaryotes? Just as organisms have a life cycle (birth-->maturation-->reproduction->-death) Each cell has an ordered sequence of activities.

3 Draw cell cycle on board. Most cells spend 90 % of life span in interphase: growth & synthesis Remaining ~10% in M phase: mitosis and cell division (aka cytokinesis)

4 LE 12-5 G1G1 G2G2 S (DNA synthesis) INTERPHASE Cytokinesis MITOTIC (M) PHASE Mitosis

5 Summary of Cell Cycle Phases –Mitotic (M) phase: mitosis and cytokinesis –Interphase G 1 phase (“1st gap”):mRNA & protein synthesis S phase: DNA synthesis aka DNA replication, DNA doubling G 2 phase (“2nd gap”):mRNA & protein synthesis

6 Regulation of cell cycle Two families of proteins control when the cell moves to different phases 1. Cyclins: regulatory subunits 2. Cyclin-dependent kinases (Cdks): catalytic subunits What is a kinase? One subunit of each complex together in a heterodimer Example: Cdk1/ cyclin B aka M-phase promoting factor (MPF) Cdk: cyclin-dependent kinase

7 LE 12-16b Degraded cyclin G 2 checkpoint S M G2G2 G1G1 Cdk Cyclin is degraded MPF Cyclin Cdk Molecular mechanisms that help regulate the cell cycle accumulation Cyclin

8 LE 12-16a MPF activity G1G1 G2G2 S MS M G2G2 G1G1 M Cyclin Time Fluctuation of MPF activity and cyclin concentration during the cell cycle Relative concentration

9 Based on the data what correlates with the cell Entering M- phase? Exiting M-phase and entering interphase? Cyclin is synthesized and complexed to Cdk1 to form active MPF --> M phase induced. Exit from M-phase correlated to cyclin degradation and MPF inhibition.

10 For unicellular organisms - Division of one cell reproduces the entire organism Focus on M phase and cell division Purpose of cell division For multicellular organisms - Embryonic and fetal growth - Growth - Repair

11 LE 12-2 Reproduction 100 µm Tissue renewal Growth and development 20 µm200 µm

12 In preparation During S phase cell duplicates genetic material (DNA) M-phase One DNA copy each moves to opposite ends of the cell Mother cell undergoes cytokinesis --> two genetically identical daughter cells. Focus on M-phase Mitosis Cytokinesis

13 Cellular Organization of the Genetic Material Genome –A cell’s endowment of DNA All its genetic information Chromosomes DNA packaged with associated proteins

14 LE 12-3 25 µm Orange: DNA Yellow/green:MT Staining of all the chromosomes or the genome in a cell

15 LE 12-4 Chromosome duplication (DNA synthesis) 0.5 µm Centromere Sister chromatids Separation of sister chromatids CentromeresSister chromatids Single chromosome

16 All eukaryotic species –Characteristic number of chromosomes located in nucleus Somatic cells - Nonreproductive e.g. muscle, epidermal cells - Two sets of chromosomes (diploid) - Undergo mitosis Germ cells or gametes – Reproductive e.g. sperm and eggs –Half as many chromosomes as somatic cells (haploid) –Undergo meiosis

17 Mitosis is conventionally divided into five phases: –Prophase –Prometaphase –Metaphase –Anaphase –Telophase Cytokinesis is well underway by late telophase [Animations and videos listed on slide following figure]

18 LE 12-6ca G 2 OF INTERPHASE PROPHASEPROMETAPHASE Blue: Chromosomes Yellow/green: MT

19 LE 12-6da METAPHASEANAPHASE TELOPHASE AND CYTOKINESIS 10 µm

20 Video: Animal Mitosis Video: Animal Mitosis Video: Sea Urchin (time lapse) Video: Sea Urchin (time lapse) Animation: Mitosis (All Phases) Animation: Mitosis (All Phases) Animation: Mitosis Overview Animation: Mitosis Overview Animation: Late Interphase Animation: Late Interphase Animation: Prophase Animation: Prophase Animation: Prometaphase Animation: Prometaphase Animation: Metaphase Animation: Metaphase Animation: Anaphase Animation: Anaphase Animation: Telophase Animation: Telophase

21 The Mitotic Spindle: A Closer Look Consists of MT –control chromosome movement during mitosis Assembly of spindle MT – at centrosome, the microtubule organizing center (MTOC) Centrosome replicates (late G2) –migrate to opposite ends poles, as spindle microtubules grow out from them Aster (a radial array of short microtubules) extends from each centrosome

22 Spindle includes the centrosomes, spindle MT, asters Some MT attach to the kinetochores of chromosomes and move chromosomes to metaphase plate

23 LE 12-7 Microtubules Chromosomes Sister chromatids Aster Centrosome Metaphase plate Kineto- chores Kinetochore microtubules 0.5 µm Overlapping nonkinetochore microtubules 1 µm Centrosome

24 LE 12-8b Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin subunits Movement of xhromosomes toward poles MT shortens--> drags chromosome toward pole

25 In anaphase – sister chromatids separate –move along the kinetochore microtubules toward opposite ends of the cell MTs shorten by depolymerization of their kinetochore ends Nonkinetochore MT –overlap and push against each other from opposite poles –Cause cellular elongation

26 –In telophase – nuclear envelopes reform around each chromosome set copy –genetically identical daughter nuclei form at opposite ends of the cell –Chromosomes decondense –MT depolymerize

27 Cytokinesis: A Closer Look In animal cells – cleavage furrow forms by action of contractile ring (actinomyosin) In plant cells –cell plate forms by fusion and elongation of vesicles between daughter cells Animation: Cytokinesis Animation: Cytokinesis

28 LE 12-9a Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells Cleavage of an animal cell (SEM)

29 LE 12-9b 1 µm Daughter cells Cell plate formation in a plant cell (TEM) New cell wall Cell plate Wall of parent cell Vesicles forming cell plate

30 LE 12-10 Nucleus Cell plate Chromosomes Nucleolus Chromatin condensing 10 µm Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell. Description of each mitotic phase

31 Prokaryotic Cell Division Binary fission –Usually one circular chromosome attached to plasma membrane via origin of replication (ori) –chromosome replicates –Daughter chromosomes move apart as cell elongates –Cell division –Mechanism distinct from mitosis.

32 LE 12-11_1 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell.

33 LE 12-11_2 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell 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 of the origin is now at each end of the cell. Origin

34 LE 12-11_3 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell 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 of the origin is now at each end of the cell. Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.

35 My genome hurts! It’s time to ask some questions.

36 Regulation of Eukaryotic Cell Cycle Checkpoint controls

37 LE 12-14 G 1 checkpoint G1G1 S M M checkpoint G 2 checkpoint G2G2 Control system (pauses if DNA is damaged or incompletely replicated) (pauses if DNA is damaged) (pauses if any kinetochores are not attached to MT) (aka spindle checkpoint)

38 For many cells G 1 checkpoint most important one Go-ahead signal (no damaged DNA) at the G 1 checkpoint --> cell completes the S, G 2, and M phases and divides e.g. skin cells, cells of gut lining and mouth No go-ahead signal Cells exits G 1 and enters quiescent state of G 0 No cell division e.g. nerve cells

39 LE 12-15 G1G1 G 1 checkpoint G1G1 G0G0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. 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.

40 Internal and External Signals at the Checkpoints Examples: Internal –Attachment of spindle to kinetochore (spindle checkpoint) –What happens if no attachment occurs? Arrest in metaphase; cell delays anaphase External –Growth factors secreted by neighboring cells –e.g. platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

41 LE 12-17 Petri plate Scalpels Without PDGF With PDGF Without PDGF With PDGF 10 mm Day 0 Day 4 Dissociate tissue into cells What did PDGF induce?

42 Other examples of external signals –Density-dependent inhibition (or contact inhibition): -crowded cells stop dividing –Anchorage dependence: -cells must be attached to a substratum in order to divide

43 LE 12-18a Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells Note: each cell is anchored to plastic substratum.

44 Cancer cells are NOT: –Density or anchorage dependent

45 LE 12-18b Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells 25 µm

46 Loss of Cell Cycle Controls in Cancer Cells Do not respond normally to the body’s control mechanisms Form tumors, masses of abnormal cells within otherwise normal tissue - Benign if stay at original site - Malignant if migrate into other parts of body (metastisis)

47 LE 12-19 Cancer cell Blood vessel Lymph vessel Tumor Glandular tissue Metastatic tumor 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. A small percentage of cancer cells may survive and establish a new tumor in another part of the body.

48 What triggers cancerous growth? Chemicals e.g. in smoke and soot, ionizing radiation, certain RNA- and DNA containing viruses e.g. HIV, hepatitis B, papilloma virus; normal metabolic damage Common property: Mutagenic: induce changes in the genome that cause: - over-expression of oncogenes, which encode proteins that push cell cycle forward - under-expression of tumor-suppressor genes, which encode proteins that normally slow cell cycle down

49 -Chemotherapy -Radiation -Surgery -Inhibitors of oncogenes -Gene therapy -Immunotherapy -Anti-angiogenesis therapy (block blood supply to tumor) How do these treatments stop cancer? Can they have negative side-effects,too? Tumor Treatments:


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