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B.Sc. Microbiology/Biotech II Cell biology and Genetics Unit 2 cell cycle


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Mitosis, meiosis, cell cycle regulation, cancer

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B.Sc. Microbiology/Biotech II Cell biology and Genetics Unit 2 cell cycle

  1. 1. Cell biology and genetics Unit 2 Cell cycle and Cancer Rai University, Ahmedabad
  2. 2. 2 Cell Division All cells are derived from pre- existing cells New cells are produced for growth and to replace damaged or old cells Differs in prokaryotes (bacteria) and eukaryotes (protists, fungi, plants, & animals)
  3. 3. 3 Keeping Cells Identical The instructions for making cell parts are encoded in the DNA, so each new cell must get a complete set of the DNA molecules
  4. 4. 4 DNA Replication  DNA must be copied or replicated before cell division  Each new cell will then have an identical copy of the DNA Original DNA strand Two new, identical DNA strands 1
  5. 5. 5 Identical Daughter Cells Parent Cell Two identical daughter cells 2
  6. 6. 6 Prokaryotic Chromosome  The DNA of prokaryotes (bacteria) is one, circular chromosome attached to the inside of the cell membrane 3
  7. 7. 7 Eukaryotic Chromosomes  All eukaryotic cells store genetic information in chromosomes  Most eukaryotes have between 10 and 50 chromosomes in their body cells  Human body cells have 46 chromosomes or 23 identical pairs
  8. 8. 8 Compacting DNA into Chromosomes  DNA is tightly coiled around proteins called histones 4
  9. 9. 9 Chromosomes in Dividing Cells Duplicated chromosomes are called chromatids & are held together by the centromere Called Sister Chromatids 5
  10. 10. 10 Karyotype  A picture of the chromosomes from a human cell arranged in pairs by size  First 22 pairs are called autosomes  Last pair are the sex chromosomes  XX female or XY male
  11. 11. 11 Cell Reproduction
  12. 12. 12 Types of Cell Reproduction  Asexual reproduction involves a single cell dividing to make 2 new, identical daughter cells  Mitosis & binary fission are examples of asexual reproduction  Sexual reproduction involves two cells (egg & sperm) joining to make a new cell (zygote) that is NOT identical to the original cells  Meiosis is an example
  13. 13. 13 Cell Division in Prokaryotes  Prokaryotes such as bacteria divide into 2 identical cells by the process of binary fission  Single chromosome makes a copy of itself  Cell wall forms between the chromosomes dividing the cell Parent cell 2 identical daughter cells Chromosome doubles Cell splits 6
  14. 14. 14 The Cell Cycle
  15. 15. 15 Five Phases of the Cell Cycle G1 - primary growth phase S – synthesis; DNA replicated G2 - secondary growth phase collectively these 3 stages are called interphase M - mitosis C - cytokinesis
  16. 16. 16 Interphase - G1 Stage 1st growth stage after cell division Cells mature by making more cytoplasm & organelles Cell carries on its normal metabolic activities
  17. 17. 7 Interphase – S Stage Synthesis stage DNA is copied or replicated Two identica l copies of DNA Original DNA
  18. 18. 18 Interphase – G2 Stage 2nd Growth Stage Occurs after DNA has been copied All cell structures needed for division are made (e.g. centrioles) Both organelles & proteins are synthesized
  19. 19. 19 Mitosis
  20. 20. 20 Mitosis  Division of the nucleus  Also called karyokinesis  Only occurs in eukaryotes  Has four stages  Doesn’t occur in some cells such as brain cells 8
  21. 21. 21 Early Prophase  Chromatin in nucleus condenses to form visible chromosomes  Mitotic spindle forms from fibers in cytoskeleton or centrioles (animal) Chromosomes
  22. 22. 22 Late Prophase  Nuclear membrane & nucleolus are broken down  Chromosomes continue condensing & are clearly visible  Spindle fibers called kinetochores attach to the centromere of each chromosome  Spindle finishes forming between the poles of the cell
  23. 23. 23 Review of Prophase What the cell looks like
  24. 24. 24 Spindle Fibers  The mitotic spindle form from the microtubules in plants and centrioles in animal cells  Polar fibers extend from one pole of the cell to the opposite pole  Kinetochore fibers extend from the pole to the centromere of the chromosome to which they attach  Asters are short fibers radiating from centrioles
  25. 25. 25 Metaphase Chromosomes, attached to the kinetochore fibers, move to the center of the cell Chromosomes are now lined up at the equator Pole of the Cell Equator of Cell 9
  26. 26. 26 Review of Metaphase What the cell looks like What’s occurring
  27. 27. 27 Anaphase  Occurs rapidly  Sister chromatids are pulled apart to opposite poles of the cell by kinetochore fibers 10
  28. 28. 28 Anaphase Review What the cell looks like What’s occurring 11
  29. 29. 29 Telophase Sister chromatids at opposite poles Spindle disassembles Nuclear envelope forms around each set of sister chromatids Nucleolus reappears CYTOKINESIS occurs Chromosomes reappear as chromatin
  30. 30. 30 Comparison of Anaphase & Telophase
  31. 31. 31 Cytokinesis Means division of the cytoplasm Division of cell into two, identical halves called daughter cells In plant cells, cell plate forms at the equator to divide cell In animal cells, cleavage furrow forms to split cell
  32. 32. 32 Daughter Cells of Mitosis  Have the same number of chromosomes as each other and as the parent cell from which they were formed  Identical to each other, but smaller than parent cell  Must grow in size to become mature cells (G1 of Interphase)
  33. 33. 33 Eukaryotic Cell Division  Used for growth and repair  Produce two new cells identical to the original cell  Cells are diploid (2n) Chromosomes during Metaphase of mitosis Prophase Metaphase Anaphase Telophase Cytokinesis 12
  34. 34. 34 Mitosis Animation
  35. 35. 35 Uncontrolled Mitosis  If mitosis is not controlled, unlimited cell division occurs causing cancerous tumors  Oncogenes are special proteins that increase the chance that a normal cell develops into a tumor cell Cancer cells 13
  36. 36. 36 Meiosis Formation of Gametes (Eggs & Sperm)
  37. 37. 37 Facts About Meiosis  Preceded by interphase which includes chromosome replication  Two meiotic divisions --- Meiosis I and Meiosis II  Called Reduction- division  Original cell is diploid (2n)  Four daughter cells produced that are monoploid (1n)
  38. 38. 38 Facts About Meiosis  Daughter cells contain half the number of chromosomes as the original cell  Produces gametes (eggs & sperm)  Occurs in the testes in males (Spermatogenesis)  Occurs in the ovaries in females (Oogenesis)
  39. 39. 39  Start with 46 double stranded chromosomes (2n) After 1 division - 23 double stranded chromosomes (n) After 2nd division - 23 single stranded chromosomes (n)  Occurs in our germ cells that produce gametes More Meiosis Facts
  40. 40. 40 Why Do we Need Meiosis?  It is the fundamental basis of sexual reproduction  Two haploid (1n) gametes are brought together through fertilization to form a diploid (2n) zygote
  41. 41. 41 Replication of Chromosomes  Replication is the process of duplicating a chromosome  Occurs prior to division  Replicated copies are called sister chromatids  Held together at centromere Occurs in Interphase 14
  42. 42. 42 A Replicated Chromosome Homologs (same genes, different alleles) Sister Chromatids (same genes, same alleles) Gene X Homologs separate in meiosis I and therefore different alleles separate.
  43. 43. 43 Meiosis Forms Haploid Gametes  Meiosis must reduce the chromosome number by half  Fertilization then restores the 2n number from mom from dad child meiosis reduces genetic content too much! The right number!
  44. 44. 44 Meiosis: Two Part Cell Division Homologs separate Sister chromatids separate Diploid Meiosis I Meiosis II Diploid Haploid
  45. 45. 45 Meiosis I: Reduction Division Nucleus Spindle fibers Nuclear envelope Early Prophase I (Chromosome number doubled) Late Prophase I Metaphase I Anaphase I Telophase I (diploid)
  46. 46. 46 Prophase I Early prophase Homologs pair. Crossing over occurs. Late prophase Chromosomes condense. Spindle forms. Nuclear envelope fragments.
  47. 47. • Prophase I • It is the longest phase of meiosis. During prophase I, DNA is exchanged between homologous chromosomes in a process called homologous recombination. This often results in chromosomal crossover. The new combinations of DNA created during crossover are a significant source of genetic variation, and may result in beneficial new combinations of alleles. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatics, with one chromosome coming from each parent. The process of pairing the homologous chromosomes is called synapses. At this stage, non-sister chromatids may cross-over at points called chiasmata 47
  48. 48. 48 Tetrads Form in Prophase I Homologous chromosomes (each with sister chromatids) Join to form a TETRAD Called Synapsis
  49. 49. 49 Crossing-Over  Homologous chromosomes in a tetrad cross over each other  Pieces of chromosomes or genes are exchanged  Produces Genetic recombination in the offspring 15
  50. 50. 50 Metaphase I Homologous pairs of chromosomes align along the equator of the cell
  51. 51. 51 Anaphase I Homologs separate and move to opposite poles. Sister chromatids remain attached at their centromeres.
  52. 52. 52 Telophase I Nuclear envelopes reassemble. Spindle disappears. Cytokinesis divides cell into two.
  53. 53. 53 Meiosis II Only one homolog of each chromosome is present in the cell. Meiosis II produces gametes with one copy of each chromosome and thus one copy of each gene. Sister chromatids carry identical genetic information. Gene X
  54. 54. 54 Meiosis II: Reducing Chromosome Number Prophase II Metaphase II Anaphase II Telophase II 4 Identical haploid cells
  55. 55. 55 Prophase II Nuclear envelope fragments. Spindle forms.
  56. 56. 56 Metaphase II Chromosomes align along equator of cell.
  57. 57. 57 Anaphase II Sister chromatids separate and move to opposite poles. Equator Pole
  58. 58. 58 Telophase II Nuclear envelope assembles. Chromosomes decondense. Spindle disappears. Cytokinesis divides cell into two.
  59. 59. 59 Results of Meiosis Gametes (egg & sperm) form Four haploid cells with one copy of each chromosome One allele of each gene Different combinations of alleles for different genes along the chromosome
  60. 60. 60 Comparing Mitosis and Meiosis
  61. 61. 61 Mitosis Meiosis Number of divisions 1 2 Number of daughter cells 2 4 Genetically identical? Yes No Chromosome # Same as parent Half of parent Where Somatic cells Germ cells When Throughout life At sexual maturity Role Growth and repair Sexual reproduction Comparison of Divisions
  62. 62. 62 Cell cycle regulation and Cancer
  63. 63. Cell cycle regulation • The timing and rates of cell division in different parts of an animal or plant are Crucial for normal growth, development, and maintenance. • The frequency of cell division varies with cell type. • Some human cells divide frequently throughout life (skin cells), others have the ability to divide, but keep it in reserve (liver cells), and mature nerve and muscle cells do not appear to divide at all after maturity.
  64. 64. A molecular control system drives the cell cycle • The cell cycle appears to be driven by specific chemical signals in the cytoplasm. • Fusion of an S phase cell and a G1 phase cell induces the G1 nucleus to start S phase. • Fusion of a cell in mitosis with one in interphase induces the second cell to enter mitosis
  65. 65. • The distinct events of the cell cycle are directed by a distinct cell cycle control system. • These molecules trigger and coordinate key events in the cell cycle. • The control cycle has a built-in clock, but it is also regulated by external adjustments and internal controls.
  66. 66. Checkpoints of cell cycle • A checkpoint in the cell cycle is a critical control point where stop and go signals regulate the cycle. • Three major checkpoints are found in the G1, G2, and M phases.
  67. 67. G1 Checkpoint • For many cells, the G1 checkpoint, the restriction point in mammalian cells, is the most important. • If the cell receives a go-ahead signal, it usually completes the cell cycle and divides. • If it does not receive a go-ahead signal, the cell exits the cycle and switches to a nondividing state, the G0 phase. • Most human cells are in this phase. • Liver cells can be “called back” to the cell cycle by external cues (growth factors), but highly specialized nerve and muscle cells never divide.
  68. 68. • Rhythmic fluctuations in the abundance and activity of control molecules pace the cell cycle. • Some molecules are protein kinases that activate or deactivate other proteins by phosphorylating them. • The levels of these kinases are present in constant amounts, but these kinases require a second protein, a cyclin, to become activated. • Levels of cyclin proteins fluctuate cyclically. • The complex of kinases and cyclin forms cyclindependent kinases (Cdks).
  69. 69. G2 Checkpoint • The G2 checkpoint prevents cells from entering mitosis when DNA is damaged • Providing an opportunity for repair and stopping the proliferation of damaged cells. • G2 checkpoint helps to maintain genomic stability, it is an important focus in understanding the molecular causes of cancer.
  70. 70. Spindle assembly checkpoints • During mitosis and meiosis, the spindle assembly checkpoint acts to maintain genome stability by delaying cell division until accurate chromosome segregation can be guaranteed. • Accuracy requires that chromosomes become correctly attached to the microtubule spindle apparatus via their kinetochores. • When not correctly attached to the spindle, kinetochores activate the spindle assembly checkpoint network, which in turn blocks cell cycle progression. • Once all kinetochores become stably attached to the spindle, the checkpoint is inactivated, which alleviates the cell cycle block and thus allows chromosome segregation and cell division to proceed.
  71. 71. Apoptosis • Apoptosis, or programmed cell death, is a normal occurrence in which an orchestrated sequence of events leads to the death of a cell. • Death by apoptosis is a neat, orderly process characterized by the overall shrinkage in volume of the cell and its nucleus, the loss of adhesion to neighboring cells, the formation of blebs at the cell surface, the dissection of the chromatin into small fragments, and the rapid engulfment of the “corpse” by phagocytosis.
  72. 72. • Because it is a safe and orderly process, apoptosis might be compared to the controlled implosion of a building using carefully placed explosives as compared to simply blowing up the structure without concern for what happens to the flying debris.
  73. 73. • It has been estimated that 1010–1011 cells in the human body die every day by apoptosis. • For example, apoptosis is involved in the elimination of cells that have sustained irreparable genomic damage.
  74. 74. 16
  75. 75. References • Images references: 1. 2. 3. 4. 5. 6. 7. 8. mitosis 9. &menuType=1&action=view&type=&name=&linkpageID=113784 10. 11. 12. 13. 14. 15. 16.
  76. 76. References • Reading references: • Cell and Molecular Biology, 6th Ed By Karp • Molecular Cell Biology by Lodish 5th Edition