CELL DIVISION

● Unicellular organisms
EUKARYOTIC – Creates duplicate offspring
CELL DIVISION ● Multicellular organisms
– Growth
– Development
– Repair

EUKARYOTIC GENOME EUKARYOTIC GENOME

(human)
about 3.3 billion nucleotide pairs
in a “haploid” genome PROBLEM:
about 100,000 genes NEED TO USE, DUPLICATE
AND THEN SEPARATE A LOT
MORE INFORMATION
LOTS MORE THAN A
PRECISELY
PROKARYOTE

EUKARYOTIC EUKARYOTIC
CHROMOSOME CHROMOSOME
● LINEAR ● MULTIPLE - many chromosomes
– one long molecule of DNA with two – human = 46 ; goldfish = 94; fruitfly = 8
ends • each species has a characteristic number

• contains genetic information in a linear – may come in sets

sequence • diploid = pairs of chromosomes
– each chromosome contain 1,000s of genes
• genes contained are in specific location and are
specific for the chromosome

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 EUKARYOTIC
CHROMOSOME EUKARYOTIC CHROMOSOME
● COMPLEXED
TELOMERE CENTROMERE
– associated with many types of proteins kinetochore
• give structure to chromosome
– chromatin = DNA-protein complex
– highly folded and coiled
• coiling increases when cell enters mitosis LONG ARM SHORT ARM
• degree of coiling related to gene activity during
interphase
before DNA replication

EUKARYOTIC
CHROMOSOME CELL CYCLE
● ORDERED SEQUENCE OF EVENTS
centromere
BETWEEN:
– The time a cell divides to form two
daughter cells, and
– The time those daughter cells DIVIDE
sister chromatids ● includes doubling of cytoplasm, cellular
organelles and DNA

CELL CYCLE
STARTING POINT

G1
M

G2

G1 + S + G2 = INTERPHASE

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 INTERPHASE CELL-CYCLE CONTROL
G1
first growth phase ● SYSTEM OF CHECKPOINTS
– BASED ON A CYCLIC SET OF
MOLECULES
● general growth and metabolism
– organelles replicate
● increase proteins and RNA
• but not DNA
● centrioles replicate (in animals)

INTERPHASE
G1

● must make decision to divide

– restriction point
• related to cytoplasm/genome volume
• determined by environmental and
developmental conditions
● commits cell to rest of cell cycle

INTERPHASE CELL CYCLE

G1
G1
M
● DIFFERENTIATION MAY OCCUR
S
–(go to G0) G0
• MUSCLE G2
• NERVE

G1 + S + G2 = INTERPHASE

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 G1 G1
the decision to divide the decision to divide
● decision may require a specific ● decision may be inhibited by cell contact
GROWTH FACTOR or cell density
– example: wound healing – density-dependent inhibition
• wound: platelets in blood fragment ● decision inhibited by lack of adhesion
to release PDGF (platelet derived – most unanchored cells do not divide
growth factor ) ● nutrient levels must be acceptable
• stimulates fibroblasts to divide – cell size and cell density

G1
INHIBITIONS TO DIVISION
the decision to divide
● cell contact or cell density ● signalled by activation of several
– density-dependent inhibition cyclin-dependent protein kinases (Cdk)
● anchorage dependence (adherence)
– most unanchored cells do not divide
● nutrient levels must be acceptable
– cell size and cell density

CELL CYCLE INTERPHASE

S phase
MAKE DNA? DNA SYNTHESIS
G1
M

S
● Exact doubling of DNA amount in cell
● All chromosomes replicated
G2
restriction point
● THEREFORE: information content of
cell DNA accurately copied
G1 + S + G2 = INTERPHASE

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 G2
CELL CYCLE SECOND GROWTH PHASE

M G1
● Some limited continued growth
S ● synthesis of proteins required for
G2 mitosis
DNA
DOUBLED

G1 + S + G2 = INTERPHASE

CYCLICAL CHANGES IN MOLECULES HOW DOES THE CELL KNOW

DURING CELL CYCLE WHEN TO ENTER MITOSIS?

G1 S G2 M G1 S G2 M
● availability of proteins required for
mitosis
● TRIGGER = MPF PROTEIN
– maturation promoting factor
DNA

PROT
RNA

MPF MPF
cyclin-Cdk complex cyclin-Cdk complex
● protein kinase ● CYCLIN + Cdk = MPF
– phosphorylates other proteins – TRIGGERS MITOSIS BY CASCADE OF
• Phosphorylation usually turns “on” protein PHOSPHORYLATION
activity by changing conformation – ACTIVATES CYCLIN-DEGRADING
● active form composed of two proteins: ENZYME
– CYCLIN
– Cdk

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 Cdk = Cyclin dependent kinase

● cell-division control
● concentration constant throughout cell
cycle
● recycled at end of mitosis

CHANGES IN CYCLIN AND

CYCLIN MPF DURING CELL CYCLE

● destroyed at end of mitosis

● produced throughout cell cycle
– therefore concentration increase
● as concentration increases, binds with
Cdk to form active MPF (cyclin-Cdk
complex)

WHAT ABOUT THE CELL AT

CELL JUST BEFORE END OF G2
MITOSIS ● nucleus present with nuclear envelope
● nucleolus present in nucleus
UNCONDENSED ● chromosomes duplicated (not condensed)
CHROMATIN ● two pairs of centrioles (animals)
IN NUCLEUS
● microtubule “asters” may be seen around
centrioles
● high levels of MPF starting kinase
SPECIFIC CHROMOSOMES NOT VISIBLE cascade

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 MITOSIS
CELL CYCLE
M PHASE
M G1 ● PROCESS OF EQUAL DISTRIBUTION
BEGIN OF CHROMOSOMES
DIVISION
S
– karyokinesis
G2
● PROCESS OF DISTRIBUTION OF
CELL COMPONENTS
– cytokinesis
G1 + S + G2 = INTERPHASE

MITOSIS PROPHASE
SEVERAL STAGES
Prophase
● CHROMATIN BEGINS TO CONDENSE
Prometaphase – chromosomes become visible
CONTINUOUS – nucleoli disappear
Metaphase DYNAMIC ● CENTRIOLES MIGRATE TOWARDS POLES (in
PROCESS
animals)
Anaphase – pairs = centrosome
● SPINDLE BEGINS TO APPEAR
Telophase – formation occurs at centrosome
two equal daughter cells • MTOC = microtubule organizing center

centrioles CHROMOSOMES
IN PROPHASE
nucleus
spindle CONSIST OF
TWO IDENTICAL
SISTER CHROMATIDS
aster chromosomes
JOINED AT CENTROMERE

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centrioles
and
aster PROMETAPHASE
● NUCLEAR MEMBRANE BEGINS TO
DISAPPEAR
spindle ● CENTRIOLES AT POLES
● SPINDLE FORMED
– microtubules interact with chromosomes
● CHROMOSOMES BEGIN TO MOVE

SPINDLE
● COMPOSED OF MICROTUBULES
● SPINDLE FIBERS = bundles of
equator microtubules
– kinetochore microtubules
• attached to centromere region
– non-kinetochore microtubules
• act to elongate the cell

kinetochore

kinetochore
fibers

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 kinetochore centromere

non-kinetochore
fibers

astral
microtubules

centrioles

CHROMOSOMES
DO LOOK LIKE THIS
BY METAPHASE

CONDENSED TWO SISTER

CHROMATIDS

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 METAPHASE
● CHROMOSOMES MOVED TO
EQUATOR
– Metaphase plate
– Centromeres aligned at equator
● SPINDLE AT GREATEST LEVEL
– centrosomes at POLES

ANAPHASE
● DOES NOT START UNTIL ALL
CHROMOSOMES ARE ATTACHED TO
SPINDLE
– APC (ANAPHASE PROMOTING COMPLEX)

ANAPHASE
● CYCLIN BEGINS TO DEGRADE
● PROTEOLTIC ENZYMES CAUSE
CENTROMERES SPLIT
● SISTER CHROMATIDS SEPARATE
● KINETOCHORE MICROTUBULES
SHORTEN
● CELL ELONGATES
ANAPHASE
● CENTROMERES SPLIT
● SISTER CHROMATIDS SEPARATE
– move towards opposite poles
– V-shape
● KINETOCHORE MICROTUBULES
SHORTEN
– at point of kinetochore attachment
● CELL ELONGATES
– sliding of non-kinetochore microtubules

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CHROMOSOME
(one chromatid) MOVEMENT OF CHROMOSOMES

● attachment of microtubules at
kinetochore
● loss of tubulin subunits
– at (+) microtubule end
• end of kinetochore attachment

CHROMOSOME
(one chromatid)

tubulin
subunits
kinetochore kinetochore
microtubule microtubule

Figure 11.8

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 TELOPHASE
● FURTHER ELONGATION OF CELL
● DAUGHTER NUCLEI FORM
● NUCLEOLI REAPPEAR
● CHROMATIN UNCOILS AND
CHROMOSOMES BECOME DIFFUSE
● CYTOKINESIS OCCURRING

CYTOKINESIS
● PROCESS OF CYTOPLASMIC
DIVISION
● NOT EXACT
– SOMETIMES DESIGNED TO BE VERY
UNEQUAL
• YEAST BUDDING

CYTOKINESIS CYTOKINESIS
PROCESS OF CELL SEPARATION PROCESS OF CELL SEPARATION

● ANIMALS (OUT --> IN) [elastic] ● ANIMALS (OUT --> IN) [elastic]
– cleavage furrow / contractile ring – cleavage furrow / contractile ring
• contractile ring = actin microfilaments
• ring breaks remains of spindle

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 CYTOKINESIS TELOPHASE IN
PROCESS OF CELL SEPARATION PLANT CELLS
● PLANTS (IN --> OUT) [rigid]
– cell plate - fused vesicles RIGID
– cell wall forms between two membranes of CELL
cell plate WALL

CELL PLATE

MITOSIS WITHOUT
CYTOKINESIS? AFTER CYTOKINESIS
● SOMETIMES;
result: multinucleated cell
– some slime molds --> plasmodium RETURN TO INTERPHASE
– some embryos --> fruit flies --> syncitium
– some algae and fungi --> coenocytic plant G1
body CONTINUE THE CELL CYCLE
– seed of flowering plants
– muscle cells

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 LOSS OF CONTROL OF
RESULTS OF MITOSIS CELL CYCLE
● CANCER = excessive division
● two daughter cells with: – unresponsive to normal control signals
– IDENTICAL genetic information • TRANSFORMATION = conversion from normal
regulation to uncontrolled growth
– SIMILAR cytoplasmic contents
● changes in cell cycle control almost
ASEXUAL PROCESS OF REPRODUCTION always “genetic”
NO VARIATION IN INDIVIDUALS – multiple changes usually required

LOSS OF CONTROL OF
CELL CYCLE
● uncontrolled production of growth
factors
– oncogenes
– tumor suppressor genes
● growth factor receptors in membranes
which are always turned on
● loss of regulation of DNA synthesis

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