The cell cycleprokaryoticeukaryotic

Control of the cell cycleloss of control- cancer

What is cell differentiation and why does it happen?what is a stem cell?

What is cloning?implications of cloning

Cell divisionprokaryotes- binary fission

one bacterium divides into twoone circular chromosome replicates

beforehandtwo identical daughter cells formcan take as little as 15 minutes

eukaryotesDNA is replicated before cell divisionsomatic cells- mitosis

two identical daughter cellsgerm cells- meiosis

gametes (sperm and eggs) whichfuse to form a zygotetakes much longer

Eukaryotic cells have several chromosomes

Number varies among species (p. 138)humans have 46 (23 pairs)

diploid organisms have pairs ofchromosomes

chromosome structure is complex

How much of that chromosome actually containsgenetic information?

How long does the cell cycle last?

Depends on the cellstem cells, embryonic cells- a few hours(embryonic cells don’t really have G1 andG2- why?)

Some cells divide very slowly

Some cells divide when inducedliverlymphocytes

Cell division

Cells grow during interphaseDNA is replicated during S phase

Division of nucleus during M phase (mitosis)Division of cytoplasm (cytokinesis)

Programmed cell death (apoptosis)

Cells divide only a certain number of timesand then die (Hayflick limit)

Role of telomeres?

Control of cell cycle- by special proteins andenzymes that act as switches

G1 checkpoint- stop, pause or go into S phasesome cells stop permanently

G2 checkpoint- will cell divide?

M checkpoint- formation of new cells

M phase drives G1 cell into mitosis, even thoughS phase has not occurred

S + G1: G1 cell starts S phaseS phase + G2: G2 will not undergo DNA synthesis

Early 1970s

I. G1 varies the most among cell typesfirst of several checkpoints is seen

What determines whether a cell will grow?

Single-celled organisms grow if enough nutrientsare present

Multicellular organisms must grow in a controlledway: growth factors

Mitogens stimulate cells to go into S phase

Many growth factors have been describedhow do they work?

Bind to tyrosine kinase receptorsActivate Ras pathway (a small membrane G

protein)↓

Cascade of phosphorylation reactions, followedby transcription

Cell passes into S phase

II. G2 checkpoint (between G2 and M)

DNA synthesis must be complete and correct

Cell may be arrested at this point

This checkpoint tends to be more importantin certain types of cells, e.g., fertilizedfrog eggs and certain strains of yeast

Cyclin-dependent kinases (Cdk)first discovered in yeast

Different kinds of cyclins; levels oscillate at different stages of cycle

Control mechanismsavailability of cyclins variesCdk must be phosphorylated

Cyclin and Cdk must be bound together to beactive

Initial cyclin-Cdk complex is inactivea series of phosphorylation and dephos-phorylation steps make it active

Complex is called MPF (mitosis-promotingfactor)

Present in both mitosis and meiosishighly conserved

MPF activates acomplex thatdegrades cyclin

G1 checkpoints

Rb prevents cell moving into S phase by bindingto a transcription factor

When Rb is phoshporylated it cannot bind socell can move into S phase

p53 prevents damaged from dividing (by inhibitingRb pathway)

Abnormalities in both genes are associated withhereditary forms of cancer

III. Spindle assembly checkpoint, betweenmetaphase and anaphase

Cell cycle can be arrested if spindle fibers arenot attached properly to chromatids

Cell growth is usually tightly regulated

Controls:contact inhibition- cells will grow to a

certain density

finite number of cell divisions

“gatekeeper genes”proto-oncogenes- stimulate growth

some make growth factorssome respond to growth factors

Types of proto-oncogenes

Growth factorsReceptors (G protein and tyrosine kinase)KinasesTranscription factorsCdk-kinases

Mutant forms, oncogenes that promote cancer,have been identified in every category

Tumor suppressors- inhibit cell growth

Cancers occur when cells grow out of control

invade and damage tissues

cells themselves may not functionproperly

How does this happen? Mutations accumulatein DNA

If mutations occur in control genes, they can’tregulate cell growth

Some defects in particular genes are associatedwith specific cancers

BRCA-1 tumor suppressor gene associated withsome inherited breast cancers

p53- tumor suppressor- associated with manycolon, bladder, breast, brain, lung cancers(about half of all cancers!)

What about this “cell destruction”?

Damaged cell undergoes apoptosis(programmed cell death)

Genetically regulated- cell has genes that bothpromote and inhibit death

How does programmed cell death differ fromdeath by injury?

Inheritance of “cancer gene”:

Each cell has 2 copies of p53. If both becomedamaged, they lose control of cell growth

If you inherit one “damaged” copy, you’re halfway there!

Mutations occur over time- cancer is more common in older people

Most cancer is NOT inherited; environmentaldamage causes most cancer

What sorts of things cause this damage?

Radiation

Toxins

Chemicals

Our bodies have many processes that repairdamaged DNA

Avoid sun exposure

Avoid smoking

Eat moderately; consume fiber. Some foodsmay help prevent cancer?

Early detection (especially important if youhave a family history of cancer)

As more is known about mechanisms ofuncontrolled cell growth, new treatmentstrategies will emerge

RadiationChemotherapyImmunotherapyKinase inhibitorsAngiogenesis inhibitorsGene replacement