Regulation of Cell Division - Application of Biology - Lecture Slides, Slides of Biology

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Regulation of Cell Division

2006-2007 Docsity.com

Coordination of cell division

• A multicellular organism needs to

coordinate cell division across different

tissues & organs

• critical for normal growth,

development & maintenance

• coordinate timing of cell division
• coordinate rates of cell division
• not all cells can have the same cell cycle

Overview of Cell Cycle Control

• Two irreversible points in cell cycle
  • replication of genetic material
  • separation of sister chromatids
• Checkpoints
  • process is assessed & possibly halted

centromere

sister chromatids

single-stranded chromosomes double-strandedchromosomes

There’s no turning back, now!

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Checkpoint control system

• Checkpoints
  • cell cycle controlled by STOP & GO chemical

signals at critical points

• signals indicate if key cellular

processes have been

completed correctly

G 1 /S checkpoint

• G 1 /S checkpoint is most critical
  • primary decision point
    • “restriction point”
  • if cell receives “GO” signal, it divides
    • internal signals: cell growth (size), cell nutrition
    • external signals: “growth factors”
  • if cell does not receive

signal, it exits cycle &

switches to G 0 phase

• non-dividing, working state

G 0 phase

• G 0 phase
  • non-dividing, differentiated state
  • most human cells in G 0 phase

M Mitosis

G Gap 1

G Resting

G Gap 2

S Synthesis

 liver cells

 in G 0 , but can be

“called back” to cell

cycle by external cues

 nerve & muscle cells

 highly specialized

 arrested in G 0 & can

never divide

“Go-ahead” signals

• Protein signals that promote cell growth &

division

• internal signals
  • “promoting factors”
• external signals
  • “growth factors”
• Primary mechanism of control
• phosphorylation
• kinase enzymes
• either activates or inactivates cell signals

Cell cycle signals

• Cell cycle controls
  • cyclins
    • regulatory proteins
    • levels cycle in the cell
  • Cdk’s
    • cyclin-dependent kinases
    • phosphorylates cellular proteins
      • activates or inactivates proteins
  • Cdk-cyclin complex
    • triggers passage through different stages of cell

cycle

activated Cdk

inactivated Cdk

Cdk / G 1 cyclin

Cdk / G 2 cyclin (MPF) G 2

S

G 1

C

M

G 2 / M checkpoint

G 1 / S checkpoint

APC

Active Inactive

Inactive Active Inactive

Active

mitosis

cytokinesis

MPF = Mitosis Promoting Factor APC = Anaphase Promoting Complex

• Replication completed
• DNA integrity

Chromosomes attached at metaphase plate

Spindle checkpoint

• Growth factors
• Nutritional state of cell
• Size of cell Docsity.com

Cyclin & Cyclin-dependent kinases

• CDKs & cyclin drive cell from one phase to next in cell cycle  proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution  the genes are basically the same in yeast, insects, plants & animals (including humans)

E2F

cytoplasm^ nucleus

cell division

nuclear membrane

growth factor

protein kinase cascade

nuclear pore

chromosome

cell surface Cdk receptor

P

P

P

P

P

Growth factor signals

Example of a Growth Factor

• Platelet Derived Growth Factor (PDGF)
  • made by platelets in blood clots
  • binding of PDGF to cell receptors stimulates cell division in fibroblast (connective tissue) - heal wounds

Don’t forget to mention erythropoietin! (EPO)

Cancer & Cell Growth

• Cancer is essentially a failure

of cell division control

• unrestrained, uncontrolled cell growth
• What control is lost?
• lose checkpoint stops
• gene p53 plays a key role in G 1 /S restriction point
• p53 protein halts cell division if it detects damaged DNA
• options: » stimulates repair enzymes to fix DNA » forces cell into G 0 resting stage » keeps cell in G 1 arrest » causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

p53 is the Cell Cycle Enforcer

DNA damage is caused by heat, radiation, or chemicals.

p53 allows cells with repaired DNA to divide.

Step 1

DNA damage is caused by heat, radiation, or chemicals.

Step 1 Step 2

Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous.

Step 3 p53 triggers the destruction of cells damaged beyond repair.

ABNORMAL p

NORMAL p

abnormal p53 protein

cancer cell cell division and repair DNA.The p53 protein fails to stop^ Step 3 Cell divides without repair to damaged DNA.

Cell division stops, and p53 triggers enzymes to repair damaged region.

Step 2

protein^ p53 DNA repair enzyme p protein

p53 — master regulator gene