CELL DIVISION: MITOSIS

• 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
Mitosis
– Cytokinesis
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)
 Types of Normal Cell Division
• There are two types of normal cell division – mitosis and
meiosis.
• Mitosis is cell division which begins in the fertilized egg (or
zygote) stage and continues during the life of the organism
in one way or another. Each diploid (2n) daughter cell is
genetically identical to the diploid (2n) parent cell.
• Meiosis is cell division in the ovaries of the female and
testes of the male and involves the formation of egg and
sperm cells, respectively. Each diploid (2n) parent cell
produces haploid (n) daughter cells.
 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
 History of Understanding
•
Cancer
Rudolf Virchow (1821-1902) – First to recognize
leukemia in mid-1800s, believing that diseased tissue
was caused by a breakdown within the cell and not from
an invasion of foreign organisms.
•  Louis Pasteur (1822-1895) – Proved Virchow to be
correct in late 1800s.
•  Virchow’s understanding that cancer cells start out
normal and then become abnormal is still used today.
•  If cancer is the study of abnormal cell division, let’s
look at normal cell division.
 Why Do Cells Undergo
Mitosis?
• Mitosis is exact nuclear division. The DNA in the
parent cell is copied exactly and then the cell nucleus
divides exactly so each of the two daughter cells has
the same kind and number of genetic base pairs
arranged in chromosomes as the parent cell.
- Mitosis is necessary because when cells reach a
surface area to volume ratio that is too small relative
to the rate of diffusion of nutrients and water into the
cell, and thus the nutritional demands of the cell
cannot be met.
• In order to address this, the cell
undergoes mitosis to form two identical,
but smaller cells, which increases the
surface area to volume ratio, and thus
the rate of diffusion can meet the
nutritional demands of the entire cell.
 MEIOSIS
• Meiosis is a type of cell division in sexually reproducing
organisms that reduces the number of chromosomes in
gametes (the sex cells, or egg and sperm). In humans,
body (or somatic) cells are diploid, containing two sets
of chromosomes (one from each parent). To maintain
this state, the egg and sperm that unite during
fertilization must be haploid, with a single set of
chromosomes. During meiosis, each diploid cell
undergoes two rounds of division to yield four haploid
daughter cells — the gametes.
Meiosis is a process where
a single cell divides twice to
produce four cells
containing half the original
amount of genetic
information.
1.1 Meiosis I
• 1.Interphase:
 The DNA in the cell is copied resulting in two
identical full sets of chromosomes.
 Outside of the nucleus are two centrosomes, each
containing a pair of centrioles; these structures are
critical for the process of cell division.
 During interphase, microtubules extend from these
centrosomes.
• Prophase I:
 The copied chromosomes condense into X-
shaped structures that can be easily seen
under a microscope.
 Each chromosome is composed of two
sister chromatids containing identical
genetic information.
 The chromosomes pair up so that both
copies of chromosome 1 are together, both
copies of chromosome 2 are together, and
so on.
.
The pairs of chromosomes may then
exchange bits of DNA in a process called
recombination or crossing over.
At the end of Prophase I the membrane
around the nucleus in the cell dissolves
away, releasing the chromosomes.
The meiotic spindle, consisting of
microtubules and other proteins, extends
across the cell between the centrioles
• Metaphase I:
 The chromosome pairs line up next to each
other along the centre (equator) of the cell.
 The centrioles are now at opposite poles of
the cell with the meiotic spindles extending
from them.
 The meiotic spindle fibres attach to one
chromosome of each pair.
• Anaphase I:
The pair of chromosomes are then
pulled apart by the meiotic spindle,
which pulls one chromosome to one
pole of the cell and the other
chromosome to the opposite pole.
In meiosis I the sister chromatids stay
together. This is different to what
happens in mitosis and meiosis II.
• Telophase I and cytokinesis:
 The chromosomes complete their move to
the opposite poles of the cell.
 At each pole of the cell a full set of
chromosomes gather together.
 A membrane forms around each set of
chromosomes to create two new nuclei.
 The single cell then pinches in the middle to
form two separate daughter cells each
containing a full set of chromosomes within
a nucleus. This process is known as
cytokinesis.
Meiosis II
•Prophase II:
Now there are two daughter cells, each with 23
chromosomes (23 pairs of chromatids).
In each of the two daughter cells the chromosomes
condense again into visible X-shaped structures that can be
easily seen under a microscope.
The membrane around the nucleus in each daughter cell
dissolves away releasing the chromosomes.
The centrioles duplicate.
The meiotic spindle forms again
• Metaphase II:
In each of the two daughter cells the
chromosomes (pair of sister chromatids)
line up end-to-end along the equator of
the cell.
The centrioles are now at opposites
poles in each of the daughter cells.
Meiotic spindle fibres at each pole of the
cell attach to each of the sister
chromatids.
• Anaphase II:
 The sister chromatids are then pulled to
opposite poles due to the action of the
meiotic spindle.
 The separated chromatids are now
individual chromosomes.
• Telophase II and cytokinesis:
 The chromosomes complete their move to
the opposite poles of the cell.
 At each pole of the cell a full set of
chromosomes gather together.
 A membrane forms around each set of
chromosomes to create two new cell
nuclei.
 This is the last phase of meiosis, however
cell division is not complete without
another round of cytokinesis.
 Crossing Over
Crossing over, as related to genetics and
genomics, refers to the exchange of DNA
between paired homologous chromosomes (one
from each parent) that occurs during the
development of egg and sperm cells (meiosis).
This process results in new combinations of
alleles in the gametes (egg or sperm) formed,
which ensures genomic variation in any offspring
produced.
Crossing Over. Crossing over is a cellular process that
happens during meiosis when chromosomes of the
same type are lined up. When two chromosomes —
one from the mother and one from the father — line up,
parts of the chromosome can be switched. The two
chromosomes contain the same genes, but may have
different forms of the genes. The mother's form of a
gene, let's say, could be moved to the father's
chromosome, and vice versa. This is a very interesting
and important biological activity; different combinations
of different gene forms are then potentially passed
down to offspring. This genetic variation helps to
increase the diversity of a species. And diversity
strengthens a species' ability to respond to changing
environments over time, and therefore evolve.