Control of Cell Division

1
Control of Cell Division

• Cultured cells divide until a single layer is
  formed then they stop.
• Remove cells neighboring cells divide until
  the void is filled...then they stop again.

2
Control of Cell Division

• Limited nutrients and/or growth factors inhibit
  division.
• Cells require adhesion to a substratum.
• Cancer cells do not respond to density-dependent
  inhibition.

3
Control of Cell Division

• G1 phase - key period in control of cell
  division. Crucial check-point late in G1, just
  before DNA synthesis (S Phase).

4
Control of Cell Division

• The RESTRICTION POINT is the go/no go decision
  -making checkpoint.
• If a go, then the cell proceeds to copy its
  DNA then divides.

5
Control of Cell Division

• Alternatively, the cell may exit the cell
  cycle switch to a non-dividing state called G0
  phase.

6

• Cell may exit cell cycle switch to a
  nondividing G0 phase.

G0
DNA SYNTHESIS
GROWTH
7
Control of Cell Division

• Most cells in the human body are in G0 phase,
  esp. nerve muscle cells.
• Liver cells can re-enter the cell cycle with
  cues such as growth factors.

8
Control of Cell Division

• CELL SIZE is important for passing the
  restriction point.

9
Control of Cell Division

• Cytoplasmic volume to genome size (amt. DNA) is
  an important criterion. You have to have enough
  soup for the new DNA to be held in.....

10
Cyclical Changes in Regulatory Proteins Function
as a Mitotic Clock

• Restriction point of no return.
• Onset of S phase commits cell to continue
  through G2 M phase divide

11
Mitotic Clock

• The following are lock-step in nature,
  chromosomes do not condense until they have
  replicated...etc.

12
Mitotic Clock

• Rhythmic fluctuations in regulatory proteins
  function as a mitotic clock that pace the
  sequential events of the cell cycle.

13
Mitotic Clock

• PROTEIN KINASES are enzymes that control the
  action of other proteins.

14

• Protein kinases activate or inactivate by
  catalyzing the transfer of a phosphate group from
  ATP to the target protein.

15

• The result is usually a shape-shift in the
  protein.

16

• CYCLINS are proteins that fluctuate in
  concentration cyclically...when a protein kinase
  is attached to a cyclin it becomes
  active....cyclin-dependent kinases (Cdks).

17
Mitotic Clock

• MPF is a M-phase promoting factor that serves as
  the master switch for a cells passage from
  interphase to mitosis (Fig. 12.14).

18
Cdk is Recycled
Accumulates
Cell Cycle
Cyclin-Degrating Enzyme is Phosphorylated
Complex Phosphorylates Proteins for
Mitosis. Interphase to M-Phase
19
Cell Cycle REVIEW

• The G1 phase is the most variable influenced
  by nutrition, growth factors, cell density,
  developmental state of the cell.

20

• A cell not reaching the restriction point will
  enter G0 permanently or temporarily (scenic
  turnout).

21
Cell Cycle REVIEW

• When all factors are favorable the restriction
  point is passed at the proper cell volume/genome
  ratio.
• Chromosome duplication occurs in S phase.

22
Cell Cycle REVIEW

• Growth in G2 of interphase
• The transition from interphase to mitosis
  requires threshold concentration of MPF.
• Cell division in M phase.

23
Abnormal Cell DivisionCANCER

• Cancer cells ignore the bodys control mechanisms
  grow as long as there are nutrients.
• They divide excessively invade other tissues.
• If unchecked, they kill the organism.

24

• Cancer cells can stop dividing at random points
  in the cell cycle.
• When growth factors are depleted, cells still
  divide.

25
CANCER

• Immortal cells in culture divide unchecked as
  long as their are nutrients normal divide 20-50X
  maximum.
• Cell line called HeLa cells from Henrietta
  Lacks, cultured in 1951..immortality!

26
CANCER

• TRANSFORMATION is the conversion from normal to
  a cancer cell, which can become a tumor if it
  proliferates.

27
CANCER

• Tumor mass of cancer cells.
• BENIGN tumor remains at its original site.
• MALIGNANT tumor becomes invasive to impair
  organs. Someone with a malignant tumor is said to
  have CANCER.

28
CANCER

• Cancer cells that spread beyond their original
  site is called METASTASIS.
• Radiation or chemotherapy are specifically
  harmful to actively dividing cells.

29
CANCER

• Alteration of genes that control cell division
  is often the cause of cancer.
• Next chapter is genes inheritance...

30
CHAPTER 12 TO DO LIST

• REVIEW KEY CONCEPTS OUTLINE
• DO SELF QUIZ
• Use Interactive CD
• WRITE DOWN QUESTION DURING LECTURE AND WHILE
  READING TO ASK YOUR TEACHING ASSISTANT.
• READ CHAPTER 13