Overview: The Key Roles of Cell Division

• The ability of organisms to reproduce best

distinguishes living things from non-living matter

• The continuity of life is based upon the

reproduction of cells, or cell division

• Cell division is integral part of cell cycle• Cell division is integral part of cell cycle

Types of cell division

• Prokaryotes

– Binary fission

• Eukaryotes

– Mitosis:

• Growth, development & repair

• Asexual reproduction (yields genetically identical cells)

• Occurs in somatic (body) cells• Occurs in somatic (body) cells

– Meiosis:

• Sexual reproduction (yields genetically different cells with half the

# of chromosomes)

• Occurs in specific reproductive cells

• Yields gametes (e.g., eggs & sperm) or spores

• Eukaryotic cell division consists of:

– Mitosis, the division of the nucleus

– Cytokinesis, the division of the cytoplasm

Mitotic 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

• A dividing cell duplicates its DNA, allocates the two copies to opposite

ends of the cell, and only then splits into daughter cells

• Every eukaryotic species has a characteristic number of chromosomes

in each cell nucleusin each cell nucleus

• Somatic (non-reproductive) cells (normally) have two sets of

chromosomes

• Gametes (reproductive cells: sperm and eggs) (and spores) have half

as many chromosomes as somatic cells

• Eukaryotic chromosomes consist of chromatin, a complex of DNA and

protein that condenses during cell division

DNA associates with special proteins to form more stable structure called chromosomes (different

proteins in prokaryotes and eukaryotes, so chromosomes built different)

Chromosomes are found inside nucleus in eukaryotes

Human - 46 chromosomes, 23 pairs (1 set of 23 from egg, 1 set of 23 from sperm)

Each chromosome contains many genes

Gene is a segment of DNA that is responsible for controlling a trait (e.g., coding for a specific protein)

You can see stained chromosomes and these can be arranged in pairs. The picture of

arranged chromosomes is called a karyotype. Chromosomes are characterized by:

Length, position of the centromere, banding pattern

M

Mitosis

G1

Gap 1

G0

Resting

G2

Gap 2

S

Synthesis

• Cell has a “life cycle”

cell is formed from

a mitotic division

Cell cycle

cell grows & matures

to divide again

cell grows & matures

to never divide again

G1, S, G2, M G0

epithelial cells,

blood cells,

stem cells

brain nerve cells

liver cells

External signals

• Growth factors

– coordination between cells

– protein signals released by body

cells that stimulate other cells to

divide

• density-dependent inhibition

– crowded cells stop dividing

– each cell binds a bit of growth factor

» not enough activator left to trigger

division in any one cell

• anchorage dependence

– to divide cells must be attached to a

substrate

» “touch sensor” receptors

nuclear membrane

growth factor

nuclear pore

Growth factor signals

E2F

nucleuscytoplasm

cell division

nuclear membrane

protein kinasecascade chromosome

Cdkcell surfacereceptor

P

P

P

P

P

• Frequency of cell division varies by cell type

– embryo• cell cycle < 20 minute

– skin cells• divide frequently throughout life

• 12-24 hours cycle

Frequency of cell division

G2

S G1

M

metaphaseprophase

anaphasetelophase

interphase (G1, S, G2 phases)

mitosis (M)

cytokinesis (C)

C

• 12-24 hours cycle

– liver cells• retain ability to divide, but keep it in reserve

• divide once every year or two

– mature nerve cells & muscle cells• do not divide at all after maturity

• permanently in G0

Prophase

Metaphase

The The

Stages of Stages of

MMitosisitosis

Interphase

Anaphase Telophase

Mitosis in animal cells

The Cell Cycle Control System

• The sequential events of the cell cycle are directed by a

distinct cell cycle control system, which is similar to a clock

• The clock has specific checkpoints where the cell cycle

stops until a go-ahead signal is received

• For many cells, the G1 checkpoint seems to be the most • For many cells, the G1 checkpoint seems to be the most

important one

G1 checkpoint

G1

SControl

system

M

M checkpoint

G2 checkpoint

G2

G1 checkpoint

G0

G1 G1

If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

If a cell does not receive a go-ahead signal at the G1

checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

Cyclin-dependent protein kinases drive

progression through the cell cycle

• Cyclin-dependent kinases

(Cdks) are inactive unless

bound to cyclins

• Active complex

phosphorylates downstream

targets

• Cyclin helps to direct Cdks to

the target proteins

Cyclin Levels

Checkpoint: DNA damage arrests

the cell cycle in G1

Apoptosis

• Programmed cell death, cell suicide

• Pathway should be activated if “something goes wrong”– Especially involving DNA/chromosome damage

• Involves proteases called caspases

• Regulated by Bcl2 and BAX– BAX homodimer promotes apoptosis, Bcl2 homodimer blocks

apoptosis

– Some cancer cells overproduce Bcl2 and are resistant to some chemotherapies and radiation treatment

• Proteins involved in cell cycle checkpoints regulate pathway

DNA damage is causedby heat, radiation, or

p53 allows cellswith repairedDNA to divide.

Step 1 Step 3p53 triggers the destruction of cells damaged beyond repair.

NORMAL p53

Cell division stops, and p53 triggers enzymes to

Step 2

DNA repair enzymep53protein

p53protein

p53 — master regulator gene

by heat, radiation, or chemicals.

DNA damage iscaused by heat,radiation, or chemicals.

Step 1 Step 2

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

of cells damaged beyond repair.

ABNORMAL p53

abnormalp53 protein

cancercell

Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.

p53 triggers enzymes to repair damaged region.

The Morphology of Apoptosis

ApoptosisA genetically controlled cell suicide pathway

Programmed cell death, is a highly regulated process that allows a cell to

self-degrade in order for the body to eliminate unwanted or dysfunctional cells.

Cytoplasm shrinks

Chromosomes condense and fragment

Nuclear membrane breaks down

Apoptotic body formation

Engulfment of the cell corpse

Apoptosis

Growth Factors and Cancer

• Growth factors influence cell cycle

– proto-oncogenes

• normal genes that become oncogenes (cancer-

causing) when mutated

• stimulates cell growth• stimulates cell growth

• if switched on can cause cancer

• example: RAS (activates cyclins)

– tumor-suppressor genes

• inhibits cell division

• if switched off can cause cancer

• example: p53

M

Mitosis

G1

Gap 1

G0

Resting

G2

Gap 2

S

Synthesis

Cancer & Cell Growth

• Cancer is essentially a failure

of cell division control

– unrestrained, uncontrolled cell growth

• What control is lost?

– checkpoint stops– checkpoint stops

– gene p53 plays a key role in G1 checkpoint

• p53 protein halts cell division if it detects damaged DNA

– stimulates repair enzymes to fix DNA

– forces cell into G0 resting stage

– keeps cell in G1 arrest

– causes apoptosis of damaged cell

• ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

Development of Cancer

• Cancer develops only after a cell experiences ~6 key mutations (“hits”)

– unlimited growth • turn on growth promoter genes

– ignore checkpoints• turn off tumor suppressor genes

– escape apoptosis– escape apoptosis• turn off suicide genes

– immortality = unlimited divisions• turn on chromosome maintenance genes

– promotes blood vessel growth• turn on blood vessel growth genes

– overcome anchor & density dependence• turn off touch censor gene

Signaling pathways are linked into Networks!

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