1. The Cell Cycle

2. The Key Roles of Cell Division:
1. Cell division functions in reproduction, growth, and repair
2. Cell division distributes identical sets of chromosomes to daughter cells

3. Reproduction, Growth and Repair:
The division of a unicellular organism reproduces an entire organism, increasing the population

4. Cell division on a larger scale can produce progeny for some multicellular organisms
this includes organisms that can grow by cuttings or by fission

5. Cell division is also central to the development of a multicellular organism that begins as a fertilized egg or zygote

6. multicellular organisms also use cell division to repair and renew cells that die from normal wear and tear or accidents

7. Cell division requires the distribution of identical genetic material (DNA) to two daughter cells
a dividing cell duplicates its DNA, moves the two copies to opposite ends of the cell, and then splits into two daughter cells

8. Cell division distributes identical sets of chromosomes to daughter cells:
a cell’s genetic information, packaged as DNA, is called its genome
a human cell must duplicate about 3 m of DNA

9. DNA molecules are packaged into chromosomes
Every eukaryotic species has a characteristic number of chromosomes in the nucleus

10. human somatic cells (body cells) have 46 chromosomes
human gametes (sperm or eggs) have 23 chromosomes

11. Each chromosome has hundreds or thousands of genes, the units that specify an organism’s inherited traits

12. Chromatin is a DNA-protein complex organized into a long thin fiber

13. After the DNA duplication, chromatin condenses, coiling and folding to make a smaller package

15. each duplicated chromosome consists of two sister chromatids which contain identical copies of the chromosome’s DNA

16. the region where the strands connect shrinks to a narrow area called the centromere

17. the sister chromatids are pulled apart and repackaged into two new nuclei

18. Mitosis - the process of the formation of the two daughter nuclei
mitosis is usually followed by division of the cytoplasm – cytokinesis

19. Gametes (eggs or sperm) are produced only in gonads (ovaries or testes)
cells in the gonads undergo meiosis - which yields four daughter cells - each with half the chromosomes of the parent

20. The Mitotic Cell Cycle:
The mitotic (M) phase of the cell cycle alternates with the much longer interphase

21. the M phase includes mitosis and cytokinesis
interphase accounts for 90% of the cell cycle

22. During interphase the cell grows by producing proteins and cytoplasmic organelles, copies its chromosomes, and prepares for cell division

23. Interphase can by subdivided into three phases:
1. G1 phase - (“first gap”) centered on growth

24. 2. S phase - (“synthesis”), when the chromosomes are copied

25. 3. G2 phase - (“second gap”), the cell completes preparations for cell division

26. After interphase the cell divides - (M)
Mitosis is broken into five subphases:
1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase

27. Interphase – (late) the chromosomes have been duplicated but are loosely packed
the centrosomes have been duplicated and begin to organize microtubules into an aster

28. Prophase - the chromosomes are tightly coiled, with sister chromatids joined together

29. the nucleoli disappear
the mitotic spindle begins to form and appears to push the centrosomes away from each other toward opposite ends (poles) of the cell

30. Prometaphase - the nuclear envelope fragments and microtubules from the spindle interact with the chromosomes

31. microtubules from one pole attach to kinetochores - special regions of the centromere

32. Metaphase - The spindle fibers push the sister chromatids until they are all arranged at the metaphase plate, an imaginary plane equidistant between the poles

33. Anaphase - the centromeres divide, separating the sister chromatids
each is now pulled toward the pole to which it is attached by spindle fibers

34. Telophase - the cell continues to elongate as free spindle fibers from each centrosome push off each other
two nuclei begin to form, surrounded by the fragments of the parent’s nuclear envelope

35. chromatin becomes less tightly coiled
cytokinesis, division of the cytoplasm, begins

36. Mitotic spindle - is a major driving force in mitosis

37. Spindle fibers composed of microtubules and proteins
come from partial disassembly of the cytoskeleton
assembly of the spindle microtubules starts in the centrosome

38. as the spindle fibers grow from them, the centrioles are pushed apart
Experiments support the hypothesis that spindle fibers shorten during anaphase from the end attached to the chromosome, not the centrosome

39. Cytokinesis:
In animals, the first sign of cytokinesis is the appearance of a cleavage furrow in the cell surface near the old metaphase plate

41. Cytokinesis in plants, which have cell walls, involves a completely different mechanism
during telophase, vesicles from the Golgi coalesce at the metaphase plate, forming a cell plate

43. Regulation of the Cell Cycle:
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

44. 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

45. Checkpoints of the cell cycle control system
Checkpoint – is a control point where stop and go-ahead signals can regulate the cycle.

46. the signals are transmitted within the cell by signal transduction pathways
animal cells generally have built-in stop signals that halt the cell cycle at checkpoints until overridden by go-ahead signals

47. these signals report whether crucial cellular processes that should have occurred by that point have in fact been completed correctly and whether or not the cell cycle should proceed

48. Three major checkpoints:
1. G1
2. G2
3. M

49. G1 Checkpoint
dubbed the “restriction point” (most important checkpoint)
if a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the G1, S, G2 and M phases and divide

50. If a cell does not receive the go-ahead signal at the G1 checkpoint, it will exit the cycle, switching into a nondividing state called G0 phase
most cells of the human body are in the G0 phase
ex. mature nerve and muscle cells, liver cells (unless damaged)

51. The cell cycle is regulated at the molecular level by a set of regulatory proteins and protein complexes
this includes kinases (enzymes that activate or inactivate other proteins by phosphorylating them) and proteins called cyclins

52. particular protein kinases give the go-ahead signals at the G1 and G2 checkpoints
many of the kinases that drive the cell cycle are present in constant concentrations in the growing cell, but usually they are in the inactive form
to be active, the kinase must be attached to a cyclin

53. Since the only way to activate the kinases is to attach a cyclin to them, they are referred to as cyclin-dependent kinases or Cdks
the activity of a Cdk rises and falls with the changes of its cyclin partner – MPF (maturation promoting factor)

54. Notice that the peaks of MPF activity correspond to the peaks of cyclin concentration

55. MPF can be thought of as “M-phase-promoting factor” because it triggers the cell’s passage past the G2 checkpoint into M phase
when cyclins that accumulate during G2 join with the Cdks, the resulting MPF complex phosporylates a variety of proteins, initiating mitosis

56. MPF causes the following to happen:
1. fragmentation of nuclear envelope (prometaphase)
2. condensation of chromosomes and spindle formation (prophase)

57. During anaphase, MPF switches itself off by initiating a process that leads to the destruction of its own cyclin
the noncyclin part MPF (Cdk) stays in the cell in its inactive form until it associates with new cyclin that is synthesized during the S and G2 phases of the next round of the cycle

59. Cancer cells have escaped from cell cycle controls
cancer cells divide excessively and invade other tissues because they are free of the body’s control mechanisms

60. cancer cells do not stop dividing when growth factors are depleted either because they manufacture their own, have an abnormality in the signaling pathway, or have a problem in the cell cycle control system

61. if and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle
cancer cell may divide indefinitely if they have a continual supply of nutrients
(In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions before they stop, age, and die)

62. Cancer cells may be “immortal”
Example: Cells (HeLa) from a tumor removed from a woman (Henrietta Lacks) in 1951 are still reproducing in culture

63. The abnormal behavior of cancer cells begins when a single cell in a tissue undergoes a transformation that converts it from a normal cell to a cancer cell
normally, the immune system recognizes and destroys transformed cells

64. however, cells that evade destruction proliferate to form a tumor - a mass of abnormal cells

65. If the abnormal cells remain at the originating site, the lump is called a benign tumor
most do not cause serious problems and can be removed by surgery

66. In a malignant tumor, the cells leave the original site to impair the functions of one or more organs
this typically fits the definition of cancer

69. In addition to chromosomal and metabolic abnormalities, cancer cells often lose attachment to nearby cells, are carried by the blood and lymph system to other tissues, and start more tumors in an event called metastasis

70. treatments for metastasizing cancers include high-energy radiation and chemotherapy with toxic drugs