CELL DIVISION AND

CELL CYCLE

Assoc. Prof. Elif Aylin Özüdoğru

Spring 2024, İstanbul
[email protected]
Cell Division

All living organisms, from the smallest bacteria to the largest

creatures, grow, develop, regenerate tissues and reproduce!

All of them produce offspring like themselves and pass on the

hereditary information that makes them what they are.
Cell division was first observed by the German embryologist
Walther Fleming in 1882, while he was examining the rapidly
dividing cells of salamander larvae.

When he looked at the cells through his primitive light

microscope, he saw minute threads within their nuclei that
appeared to be dividing lengthwise. Fleming called their division
mitosis, based on the Greek word mitos, meaning “thread.”
Cell Division and Cell Cycle
Prokaryotes divide far more simply than
do eukaryotes.
In prokaryotes, which lack a nucleus, cell
division consists of a simple procedure
called binary fission.
The cell divides into two equal or nearly
equal halves.
The genetic information, or genome exists as a single, circular,
double-stranded DNA molecule and it replicates early in the life
of the cell.

The DNA circle is attached at one point to the cytoplasmic

surface of the bacterial cell’s plasma membrane.
At a specific site on the DNA molecule called the replication
origin, a battery of more than 22 different proteins begins the
process of copying the DNA.
When these enzymes have proceeded all the way around the
circle of DNA, the cell possesses two copies of the genome.
These “daughter” genomes are attached side-by-side to the
plasma membrane.
The growth of a bacterial cell to about twice its initial size
induces the onset of cell division. A wealth of recent evidence
suggests that the two daughter chromosomes are actively
partitioned during this process.
As this process proceeds, the cell lays down new plasma
membrane and cell wall materials in the zone between the
attachment sites of the two daughter genomes. A new plasma
membrane grows between the genomes; eventually, it reaches all
the way into the center of the cell, dividing it in two. Because
the membrane forms between the two genomes, each new cell is
assured of retaining one of the genomes.
Finally, a new cell wall forms around the new membrane and cells
seperate, producing two daughter cells.
Prokaryote cells grow by
increasing in cell number
(as opposed to increasing
in size).

Replication is by binary
fision; the splitting of one
cell into two.

Therefore, bacterial
populations increase by a
factor of two (double)
every generation time.
 Cell Division and Cell Cycle

Nuclear Nucleolus Chromosomal The increased size

Golgi Nucleus
body envelope DNA
and more complex
organization of
eukaryotic genomes
Polyribosomes
Ribosome
over those of
Rough ER prokaryotes required
Cytoplasm radical changes in
Membrane protein
Plasma membrane
the process of cell
Smooth ER division. This division
Lysosome
process is
diagrammed as a cell
Microfilaments Centrioles
cycle, consisting of
Mitochondrion Microtubules five phases:
Cell Division and Cell Cycle
DNA Synthesis

Interphase

S
Synthesis

G1 G2
Gap 1 M
Mitosis Gap 2
Growth
Gene expression
Differentiation

Two Gene expression

daughter Quality control
cells

Actual division process

G1 is the primary growth S is the phase in which the
phase of the cell. For many cell synthesizes a replica of
organisms, this is the major the genome.
portion of the cell’s life span.
G2 is the second growth phase, in which preparations are made
for genomic separation. During this phase, mitochondria and other
organelles replicate, chromosomes condense, and microtubules
begin to assemble at a spindle. G1, S, and G2 together constitute
interphase, the portion of the cell cycle between cell division.
The phase called ‘mitosis’ is the phase of the cell cycle in which
the microtubular apparatus assembles, binds to the chromosomes,
and moves the sister chromatids apart. This process is the
essential step in the separation of the two daughter genomes.

Although mitosis is a continuous process, it is traditionally

subdivided into four stages: prophase, metaphase, anaphase, and
telophase.
Cytokinesis is the phase of the cell cycle when
the cytoplasm divides, creating two daughter
cells. In animal cells, the microtubule spindle
helps position a contracting ring of actin that
constricts like a drawstring to pinch the cell in
two. In cells with a cell wall, such as plant
cells, a plate forms between the dividing cells.
The time it takes to complete a cell cycle varies greatly among
organisms. Cells in growing embryos can complete their cell cycle
in under 20 minutes; the shortest known animal nuclear division
cycles occur in fruit fly embryos (8 minutes).
Because mature cells require time to grow, most of their cycles
are much longer than those of embryonic tissue.
Cell Division and Cell Cycle

Cell cycle of a typical cultured human cell takes about 24 hours:

~ 1 hour; M phase,
~ 23 hours; interphase: ~10-12 hours; S phase.
Cell Division and Cell Cycle During G (Gap) phases, the internal and
external conditions are appropriately
checked, and preparations are completed
before entering into the S phase and M
phase.

G1 phase is particularly important, and the

length of this phase varies depending on the
external conditions and extracellular signals
from other cells. If the conditions are not
suitable, the cells enter the G0 phase and
may remain here for days, months or even
years. Some cells remain in the G0 phase
until the organism dies.

Many cells in our body are always in G0 phase (neurons, skeletal muscle cells).
Some cells enter and exit the cell cycle when needed (e.g., damaged liver
cells), while some others enter the cell cycle as repetitions (e.g., fibroblasts
and lymphocytes).
Interphase: Preparing for Mitosis

Two centrosomes,
• Chromosomes are decondensed. each with centriole pairs

Nuclear
• Chromosomes, which replicated membrane
durign S phase, cannot be seen
individually as they are not
condensed yet.

• Two centrosomes have formed

by duplication of a single
centrosome. Chromosomes
Prophase: Asters (stars)

Microtubules
• The nucleoli disappears. forming mitotic spindle Sister
chromatids
• The mitotic spindle apparatus
begins to form (microtubules
extend from centrosomes). The
radial arrays of shorter
microtubules are called ‘asters’.

• Centrosomes move away from

each other (to opposite poles).
Centromere
Prophase:
Spindle Apparatus:

• Composed of microtubules originated from centrioles,

• Microtubules are formed by polymerization of tubulin proteins.

• 3 types of spindle microtubules:

• Aster microtubules are important for positioning of the
spindle apparatus,
• Polar microtubules help to “push” the poles away from each
other,
• Kinetochore microtubules attach to kinetochore at the
centromere.
Prophase: Asters (stars)
• Chromatin fibers become more
tightly coiled, condensing into Microtubules
discrete chromosomes. forming mitotic spindle Sister
chromatids

• Each duplicated chromosome

appears as two identical sister
chromatids joined at their
centromeres.

Centromere

Pair of sister chromatids

Prometaphase:
• The nuclear envelope fragments.
Nuclear membrane
• The microtubule extention invades fragmenting
the nuclear area.
• The chromosomes have become
even more condensed.
• Each of the two chromatids of
each chromosome has a
kinetochore.
Kinetochore
proteins

Mitotic
spindle
Spindle pole

Pair of sister chromatids

 Kinetochore
Prometaphase: microtubules
• Kinetochore microtubules attach
Nuclear membrane
to the kinetochores and jerk the fragmenting
chromosomes back and forth.
• Polar (non kinetochore)
microtubules interact with those
from the opposite pole of the
spindle.

Polar (non kinetochore)

microtubules Mitotic
spindle
Spindle pole
Metaphase:
Astral
• The centrosomes are now microtubule
at the opposite poles.
• The chromosomes have all
arrived at the metaphase Metaphase
plate. plate
• The kinetochores of the
sister chromotids are Polar
attached to the microtubule
kinetochore microtubules Kinetochore
coming from opposite proteins attached
Kinetochore
to centromere
poles. microtubule
Metaphase:
Anaphase: Daughter chromosomes

• Cohesin proteins are cleaved

and thus the two sister
chromatids seperate.
• Kinetochore microtubules
shorten, the two liberated
daughter chromosomes move
towards opposite ends of the
cell.
• Polar microtubules lengthen,
thus the cell elongates.
• By the end of anaphase, the
two ends of the cell have
equivalent and complete
collections of chromosomes.
Telophase and Cytokinesis:

• Chromosomes reach poles and

decondense.

• Two daughter nuclei form.

Nuclear envelops arise from
the fragments of the parent
cell’s nuclear envelope and
other portions of the
endomembrane system.

• Remaining spindle microtubules

are depolimerized.
Telophase and Cytokinesis:
• Cytokinesis follows either by formation of a cleavage furrow (in
animals) or by formation of a cell plate (in plants).
Some key points for Mitosis:

• Mitosis ultimately produces two daughter cells genetically

identical to the mother cell.
• Barring rare mutations.
• Processes requiring mitotic cell division:
• Development of multicellularity,
• Organismal growth,
• Wound repair,
• Tissue regeneration.
Sexual reproduction is the most common way for eukaryotic
organisms to produce offspring. Parents make gametes with half
the amount of genetic material (haploid). These gametes fuse
with each other during fertilization to generate a new organism.

Simple eukaryotes are isogamous; they produce gametes that are

morphologically similar.
Most eukaryotic species are heterogamous; these produce gametes
that are morphologically different.
• Sperm cells: Relatively small and mobile.
• Oocytes or ova: Usually large and nonmobile. Store large
amounts of nutrients.
• Microspores (Pollen)
• Macrospores (Ovules)
Two sets of chromosomes are present in the somatic cells of
adult individuals, making them diploid cells (Greek diploos,
“double” + eidos, “form”), but only one set is present in the
gametes, which are thus haploid (Greek haploos, “single” + ploion,
“vessel”).

After fertilization, the resulting zygote begins to divide by

mitosis. This single diploid cell eventually gives rise to all of the
cells in the adult. These cells are called somatic cells, from the
Latin word for “body.”
Gametes of opposite sex unite to form a cell (zygote) that,
dividing repeatedly by mitosis, eventually gives rise to an adult
body with some 100 trillion cells.

The zygote
and all of the
The fusion of gametes to somatic cells
form a new cell is called derived from
fertilization or syngamy. it contain two
copies of each
chromosome.
The cells that will eventually undergo meiosis to produce gametes
are set aside from somatic cells early in the course of
development. These cells are often referred to as germ-line
cells. Both the somatic cells and the gamete-producing germ-line
cells are diploid, but while somatic cells undergo mitosis to form
genetically identical, diploid daughter cells, gamete-producing
germline cells undergo meiosis, producing haploid gametes.

In animals, the
completion of meiosis
is followed soon by
fertilization. Thus,
the vast majority of
the life cycle is spent
in the diploid stage.
It was clear even to early investigators that gamete formation
must involve some mechanism that reduces the number of
chromosomes to half the number found in other cells. If it did
not, the chromosome number would double with each fertilization,
and after only a few generations, the number of chromosomes in
each cell would become impossibly large.

The number of chromosomes does not explode in this way because

of a special reduction division that occurs during gamete formation
in meiosis, producing cells with half the normal number of
chromosomes and subsequent fusion of these two ensures a
consistent chromosome number from one generation to the next.

Meiosis and fertilization together constitute a cycle of

reproduction called ‘sexual reproduction’.
How Does One Make a Haploid Gamete?
• The answer is: meiosis!
• Haploid cells are produced from diploid cells during gametogenesis.
• The chromosomes must be distributed to reduce the chromosome
number to half its original value.
• The chromosomes are sorted to assure that each chromosome (& its
genes) is represented in each gamete.
• In many ways, meiosis is a lot like mitosis. The cell goes through
similar stages and uses similar strategies to organize and separate
chromosomes. In meiosis, however, the cell has a more complex task.
It still needs to separate sister chromatids (the two halves of a
duplicated chromosome), as in mitosis. But it must also
separate homologous chromosomes, the similar but nonidentical
chromosome pairs an organism receives from its two parents.
Meiotic Cell Division (Meiosis)

Just like in mitosis, meiosis begins after a cell has progressed

through G1, S, and G2.

However, meiosis involves two successive divisions:

• Meiosis I and Meiosis II
Each of these is subdivided into:
• Prophase • Prophase I is further subdivided into periods:
• Metaphase • Leptotene
• Anaphase • Zygotene
• Telophase • Pachytene
• Diplotene
• Diakinesis
Meiotic Cell Division (Meiosis) – Periods of Prophase I

A total of 4
chromatids

A recognition
process
Meiotic Cell Division (Meiosis) – Periods of Prophase I
Meiotic Cell Division (Meiosis) – Periods of Prophase I

A 2
tetrad bivalents

A physical exchange of
chromosome pieces
Meiotic Cell Division (Meiosis) – Stages of Meiosis I
Spindle apparatus complete;
pairs of chromatids attached
to kinetochore microtubules
Unique Features of Meiosis
Meiosis has three unique features:
● synapsis,
● ● homologous recombination, and
● ● ● reduction division.

● ● ● ● ● ●
Synapsis:
The first unique feature of meiosis happens early during the first
nuclear division (Prophase I). Following chromosome replication,
homologous chromosomes pair all along their length. The process
of forming these complexes of homologous chromosomes is called
synapsis.
Homologous Recombination:
The second unique feature of meiosis is that genetic exchange
occurs between the homologous chromosomes while they are thus
physically joined. The exchange process that occurs between
paired chromosomes is called crossing over. The spots where
crossovers happen are more or less random, leading to the
formation of new, "remixed" chromosomes with unique
combinations of alleles.
Homologous Recombination:
DNA segments are exchanged between nonsister or sister
chromatids. In humans, an average of two or three such
crossover events occur per chromosome pair. Evidence of crossing
over can often be seen under the light microscope as an X-
shaped structure known as a chiasma (Greek, “cross”; plural,
chiasmata). The presence of a chiasma indicates that two
chromatids (one from each homologue) have exchanged parts.
Reduction Division
The third unique feature of meiosis is that the chromosomes do
not replicate between the two nuclear divisions, so that at the
end of meiosis, each cell contains only half the original
complement of chromosomes.
Meiotic Cell Division (Meiosis) – Stages of Meiosis I

• Bivalents are organized along the

metaphase plate.

• Homologous pairs of sister

chromatids aligned side by side:

• A pair of sister chromatids is

linked to one of the poles, and
the homologous pair is linked
to the opposite pole.
• The arrangement is random
with regards to the (blue and
red) homologues.
Meiotic Cell Division (Meiosis) – Stages of Meiosis I
Pairs of sister chromatids separate
from each other. The centromere
remains between sister chromatids.
Meiotic Cell Division (Meiosis) – Stages of Meiosis I

• Telophase I and cytokinesis of meiosis I is followed meiosis II.

• Meiosis I has reduced the number of chromosomes in the
daughter cells to the ½ the diploid number.
• However, each homolog is still composed of 2 recombinant
sister chromatids:
• The genetic content is still 2n.
• Meiosis II reduces the genetic content to n.
Meiotic Cell Division (Meiosis) – Stages of Meiosis II

1 of each type of
chromosome (n) in each
daughter cell (gamete).
Separation of Alleles During Meiosis

Gene loci (location)

A b c
Homologous pair
of chromosomes

A B c

Genotype: AA Bb cc
Homozygous for Heterozygous Homozygous for the
the dominant Recessive allele
allele
Separation of Alleles During Meiosis
Separation of Alleles During Meiosis

y yY Y Heterozygous (Yy) cell from

Prophase I
a plant with yellow seeds

Metaphase I y Y

Anaphase I
y y Y Y
Telophase I

Meiosis II y y Y Y

Haploid cells
Separation of Alleles During Meiosis
y r r
y Y Y Heterozygous diploid cell (YyRr)
to undergo meiosis
R R

y Y y Y

R r r R
Meiosis I

y y Y Y y y Y Y

R R r r r r R R
Meiosis II

y y Y Y y y Y Y

R R r r r r R R
2 Ry : 2 rY 2 ry : 2 RY
Thanks for your
patience and
attention