1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Cell Cycle

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pre-Unit Questions What types of cells undergo mitosis? What is a haploid cell? – Give an example of this type of cell What is a diploid cell? – Give an example of this type of cell True or False – the cell cycle consists of prophase, metaphase, anaphase, and telophase only. (if false, correct the statement) What are the parts of a duplicated chromosome Can you identify the following stages of mitosis

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Cell Cycle Overview: The Key Roles of Cell Division The continuity of life – Is based upon the reproduction of cells, or cell division Unicellular organisms – Reproduce by cell division 100 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). Figure 12.2 A

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Division Multicellular organisms depend on cell division for – Development from a fertilized cell – Growth – Repair 20 µm200 µm (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). Figure 12.2 B, C

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Division Cell division results in genetically identical daughter cells Cells duplicate their genetic material – Before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cellular Organization of the Genetic Material A cell’s endowment of DNA, its genetic information – Is called its genome

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Material The DNA molecules in a cell – Are packaged into chromosomes 50 µm Figure 12.3

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Material Eukaryotic chromosomes – Consist of chromatin, a complex of DNA and protein that condenses during cell division

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Distribution of Chromosomes During Cell Division In animals – Somatic cells have two sets of chromosomes diploid – Sex cells (gametes) have one set of chromosomes haploid In preparation for cell division – DNA is replicated and the chromosomes condense

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phases of the Cell Cycle The cell cycle consists of – The mitotic phase – Interphase – the cell grows, duplicates proteins, organelles and chromosomes INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5 The mitotic phase alternates with interphase

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interphase – and its subphases (preparation for cell division) G 1 phase – cell grows, produces proteins and organelles requires structural proteins and enzymes S phase – DNA synthesis (form sister chromatids) (see next slide) G 2 phase – 2 nd growth phase. During G2, organelles replicate, chromosomes get ready to condense, and microtubules start to form at centrioles. M phase –cell division and cytokinesis INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5 Mitosis – division of the nucleus Cytokinesis – division of the cytoplasm

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Duplicated Chromosomes Each duplicated chromosome – Has two sister chromatids, which separate during cell division 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids Centromeres Sister chromatids A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid 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

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Mitotic Phase – Mitosis and Cytokinesis Mitosis consists of five distinct phases – Prophase – Prometaphase 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

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis – Metaphase – Anaphase – Telophase Centrosome at one spindle pole Daughter chromosomes METAPHASEANAPHASETELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Figure 12.6

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Mitotic Spindle: A Closer Look The mitotic spindle – Is an apparatus of microtubules that controls chromosome movement during mitosis

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The mitotic spindle The spindle arises from the centrosomes – And includes spindle microtubules and asters – Within an animal cell centrosome there is a pair of small organelles, the centrioles – Unlike centrosomes in animal cells, plant cells do not have centrioles.

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic spindle An aster is an array of microtubules that has formed from the centrosome after it moves to opposite poles.

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic spindle Some spindle microtubules – Attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate CentrosomeAster Sister chromatids Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules Centrosome Chromosomes Microtubules 0.5 µm 1 µm Figure 12.7 Kinetochore microtubules attach to the kinetochore and the poles. These fibers will then attach to the mitotic spindle fibers which will move the sister chromatids towards the opposite poles

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic spindle

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Moving chromosomes In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell – Nonkinetechore microtubules from opposite poles overlap and push against each other, elongating the cell

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Movement of chromosomes In telophase – Genetically identical daughter nuclei form at opposite ends of the cell

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis Review

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis: A Closer Look In animal cells – Cytokinesis occurs by a process known as cleavage, forming a cleavage furrow Cleavage furrow Contractile ring of microfilaments Daughter cells 100 µm (a) Cleavage of an animal cell (SEM) Figure 12.9 A

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis In plant cells, during cytokinesis – A cell plate forms 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

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of Mitosis Mitosis in a plant cell 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop 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 cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 23 4 5 Nucleus Nucleolus Chromosome Chromatine condensing Figure 12.10

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Binary Fission Prokaryotes (bacteria) – Reproduce by a type of cell division called binary fission – Results in two genetically identical cells

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Binary Fission In binary fission – The bacterial chromosome replicates. Begins at the origin of replication – The two daughter chromosomes actively move apart Origin of replication E. coli cell Bacterial Chromos ome Cell wall Plasma Membrane Two copies of origin Origin Origin of replication opens up like a bubble and the two strands move in opposite directions 1 Replication continues until one copy of the origin is now at each end of the cell. 2 The cell wall grows across the middle of the cell 4 Two daughter cells result. 5 43 Each replicated strand attached itself to the cell membrane. The cell elongates, separating the replicated strands

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Evolution of Mitosis Since prokaryotes preceded eukaryotes by billions of years – It is likely that mitosis evolved from bacterial cell division mitosis is a universal eukaryotic property – All eukaryotes (except amoeba) undergo mitosis. the key molecules involved in mitosis, have homologous moleclues in prokaryotes

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Cycle Controls To grow and develop normally a plant or animal cell must be able to control the timing of cell division. The frequency of cell division – Varies with the type of cell The events are directed by a cell cycle control system

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G1 phase checkpoint The cell has a checkpoint at this phase. The cellular environment is checked and cell size. Only when conditions are right will the cell proceed into the S phase – If signal is not received it goes to a non- dividing stage called G0 phase.

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 0 Phase This is mitotic dormancy or differentiation Cells are not considered to be in the cycle of division but become differentiated or specialized in their function Cells can “mature” at this time to play a role based on the specific genes they express. Some cells remain here permanently. Some may stay here for hours, days, months. – E.g. nerve cells Some can revert back to G1, S and G2

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other Checkpoints Check points will also occur after the S phase and G2 phase.

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulators Internal Regulators – Regulate the timing inside the cell cycle, when the cell can proceed from one phase to the next. Ex. G1 to S phase External Regulators – Regulate timing external to the cell, like when it is necessary for cells to divide in general

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulation comes from protein signals Cyclins are a class of proteins that regulate the cell cycle Two main types Cyclin Dependent Protein Kinases (Cdks) Cyclins

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclins undergo a constant cycle of synthesis and degradation during cell division cyclins act as an activating protein and bind to Cdks forming a cyclin-Cdk complex This complex then acts as a signal to the cell to pass to the next cell cycle phase. Eventually, the cyclin degrades, deactivating the Cdk, thus signaling exit from a particular phase.

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Regulation-Cyclin dependent kinases Cdks – These are simply found within the cell, not synthesized – Only become active when bound with cyclins – A Cdks is an enzyme that adds negatively charged phosphate groups to other molecules in a process called phosphorylation. Through phosphorylation, Cdks signal the cell that it is ready to pass into the next stage of the cell cycle

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In General The combinations of cyclins and cyclin- dependent kinases (CDKs) work together to phosphorylate (add phosphate) and activate (or inactivate) target proteins in the steps of the cell cycle. Different combinations determine which target protein will be affected

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What are some factors that keep normal cells in “check” Growth Factors – A protein that stimulates other cells to divide Density – dependent inhibition - causes crowded cells to stop dividing (run out of nutritens) Anchorage dependence – in order to divide, cells must be attached to a substrate

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Loss of Cell Cycle Controls Cells that do not respond normally to these controls. – Cancer cells – Exhibit neither density-dependent inhibition nor anchorage dependence

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Loss of Cell Cycle Controls in Cancer Cells Cancer cells – Do not respond normally to the body’s control mechanisms – Form tumors – Benign tumors remain at the original site and are usually harmless. An abnormal mass of essentially normal cells.

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tumors Malignant tumors invade surrounding tissues and can affect one or more organs. The cells have undergone a transformation (no longer “normal”) Figure 12.19

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer Cells from a malignant tumor may split off, and travel to new locations, where they can form new tumors. The spread of cancer cells beyond their original site is called metastasis

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer Treatments Treatments for cancer include: – Radiation Causes Apoptosis – “programmed cell death” – Many cells will kill themselves for the betterment of the organisms Like cells damaged by virus Cells in the lining of the uterus – Chemotherapy

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What prevents normal cells from becoming tumor cells Genetic damage or errors are often repaired The tumor suppressor gene p53 gene – This gene stops a damaged cell just before the S phase so that it can be repaired.