cell division: mitosis

biology 1
• Why cells divide and what they have to
do to accomplish this
• Division in prokaryotes
• Division in eukaryotes
– Chromosone structure
– Phases of the cell cycle
• Cell growth factors
– Cancerous growths
 Why divide?
• Ensures persistence of genome
– Precisely replicates DNA
– Equally distributes DNA to opposite end of cell
– Seperates into two identical daughter cells
• Strategy to counter loss of SA:Vol ratio as cell
grows larger
• Permits growth and development of a
multicellular organism
• Allows replacement of damaged or dead cells

Genome = total endowment of DNA unique to each species

 • In prokaryotes, cell division is through binary
fission
• In eukaryotes, division is by mitosis. For example:

The human life cycle

Meiosis in the gonads
halves the chromosone
number

Individual inherits 46
chromosones, 23
from each parent Sperm cell
(23 chromosones)
Ovum
Mitosis produces (23 chromosones)
genetically identical
daughter cells.
Process is
responsible for Zygote
growth, development
and repair
(46 chromosones)
Fertilization restores the chromosone
number to 46
 Prokaryotes divide by binary fission
• Most genetic material incorporated into a single circular
chromosone made of double stranded DNA and
associated proteins
• Contains 1/1000 of eukaryote dna: still, highly folded and
packed into cell
• Binary fission
– Chromosone replicates into identical loops, each attached to the
plasma membrane at adjacent sites
– Between attachment sites the membrane grows and separates the
two copies of the chromosone
– Bacterium grows to twice its size and cleavage furrow develops
– Cell wall develops across bacterium between the two
chromosones
 Cell division in eukaryotes
• Chromosones consist of a DNA-protein
complex called chromatin. Proteins include
histones that aid in coiling of nucleic
material in dense, visible chromatids
• Mitosis duplicates chromosones to pairs of
sister chromatids (duplication is very
precise: only 1 error in 100,000) and sends
each replication to opposite poles of the cell
• Mitosis may be followed by cytokinesis
 The cell cycle
Interphase
• 90% of time spent in
Interphase S-phase

– G1 = first growth phrase

– S = duplication of DNA
G1 G2
– G2 = second growth phase
• 10% in dividing, or M
phase
– Mitosis - division of nucleus
– Cytokinesis Mitosis

M-phase
 G2 Interphase
• Characterized by
– Well defined nucleus bound by nuclear envelope
– Nucleoli
– A pair of centrosomes adjacent to nucleus (division
occurs in S-phase
• (in animals) a pair of centrioles in each centrosome
• (in animals) a microtubular array (aster) around each
centrosome
– Duplicated chromosones cannot be distinguished
(chromatin too loosely packed)
 Prophase
• Characterized by
– Disappearance of nucleoli
– Chromatin fibers condense into discrete
chromosones composed of two identical
sister chromatids joined at a centromere
– Formation of mitotic spindle, composed of
microtubules between the two
centrosomes
– Centrosomes move apart, migrating across
surface of nuclear envelope
 Prometaphase
• Characterized by
– Nuclear envelope fragments and dissolves
– Spindle fibers extend from each pole towards
the cell equator
– Each chromatid has a specialized center called
the kinetochore, located at the centromere
– Kinetochore microtubules attach to the
kinetochores
– Non-kinetochore microtubules from each
centrosome overlap each other
 Metaphase
• Characterized by
– Centrosomes are at opposite poles of the cell
– Chromosones migrate to the metaphase plate
– Centromeres of all chromosones are aligned on
metaphase plate
– Kinetochores of sister chromatids face opposite
poles, so that identical chromatids are attached to
kinetochore fibers radiating from opposite ends of the
parent cells
– Entire structure formed by kinetochore and non-
kinetochore fibers is termed the spindle
 Anaphase
• Characterized by
– Sister chromatids split apart into separate
chromosones, moving to opposite ends of the cell
(depolymerization of microtubules at kinetochore
end)
– Chromosones move centromere-first, moving
chromatids in a v-shape
– Poles of cell move further apart, elongating cell

At the end of anaphase, the two poles of the

cell have identical collections of chromosones
 Telophase
• Characterized by
– Non-kinetochore microtubules further elongate
the cell
– Daughter nuclei begin to form at the two poles
– Nuclear envelope forms around chromosones
from fragments of parent cell’s nuclear
envelope
– Nucleoli reappear
– Chromatin protein uncoils and chromosones
become less distinct
 Cytokinesis
• (in animal cells) Cleavage furrow forms and pinches off
the two daughter cells
– Done by a contractile ring of microtubules on cytoplasm side of
membrane
• (in plant cells) a cell plate (old metaphase plate) grows
between the two daughter cells.
– Cell membrane grows either side along length of cell plate,
which becomes the cell wall

By end of cytokinesis
– Two separate daughter cells with genetically identical nuclei
 Control of cell division
• Cues include
– Growth factors may bind with membrane receptors
to promote division
– Density dependent inhibition (affected by nutrients
and space)
– G1 phase has a ‘point of no return’, termed the
restriction point, passed which a cell must go into the
s-phase
• If a cell doesn’t go past restriction point, goes into G 0 phase
- stasis
– Cell size: ratio of cytoplasm to genome ration must
be high enough to allow cell to go past restriction
point
 The mitotic clock
• Still mostly unknown process: the onset of S-phase
appears to commit cell to G2 and m-phase
• Cell cycle events are synchronized by rhythmic
changes in regulatory proteins called protein
kinases that catalyze the phosphorylation of a
target protein by ATP
• Phosphorylation activates or inhibits the target
protein’s activity
• Cyclical changes in kinase activity are controlled by
a second group of regulatory proteins called cyclins
• Protein kinases that regulate cell cycles
are cyclin-dependent kinases (Cdks)
• Cdk concentration stay the same
throughout the cell cycle. However, its
activity varies
• For example active MPF (maturation
promoting factor)
– Phosphorylates chromatin proteins, causing
chromosones to condense in prophase
– Phosphorylation of nuclear envelope in
prometaphase promotes fragmentation
 • Cyclin, produced throughout the cell cycle,
accululates during interphase
• Cyclin combines with cdk to make active
MPF, which peaks in concentration with the
peak in cyclin
• MPF initiates mitosis
• At the end of mitosis, MPF activates an
enzyme that destroys cyclin
mitosis Interphase mitosis Interphase mitosis

Relative
concentration

time
 Cancers - cells lacking division control
• Cancerous cells do not respond to standard cellular
controls, growing and dividing until nutrients are
exhausted
• Cells that become cancerous are said to have
transformed
• Immune system usually destroys such cells, but if
not, cancerous cells coalesce to tumors
• If cells remain at the tumor, then the tumor is benign
• If cells spread out, then tumor is malignant - spread is
called metastasis
• Cause of cancerous cells is probably caused by
alteration of genes that control cell division