Cell Cycle, mitosis and meiosis

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 Cell Cycle
• Eukaryotic somatic cells that have the
capacity to divide are understood to be in
the cell cycle
• Time from the birth of a new daughter cell
until it is capable of cell division to form
two new daughter cells is the cell cycle
• Can be divided into TWO broad stages:
– Interphase (Period between cell division)
– Mitosis (Period of actual cell division)
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 Cell cycle

Interphase Mitosis
• Maximum time is spent • Period when the cell
in this phase. Varies from actually divides to form
one cell type to another two new daughter cells
• Cell grows during this • Time spent in mitosis
phase and is ready for is about 2-4 hours and
mitosis at the end of is usually constant
interphase 3
 Types of cells
• Labile cells: Multiply throughout life. Cells
of skin, GIT, epithelial cells
• Stable cells: Are quiescent (Go phase).
Can divide if appropriately stimulated.
Liver cells
• Permanent cells: Have lost the capacity to
divide. They are permanently in Go phase.
Neurons, Cardiac muscle cells

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 Stages of cell cycle
• Interphase (time between cell division)
– G1 phase (Go phase)
– S phase
– G2 phase
• Mitosis (Stage of cell division)
– Prophase
– Metaphase
– Anaphase
– Telophase
– Cytokinesis (Cell division)
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Stages of cell cycle

Go

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 Stages of cell cycle
• G1 (Gap 1 or Growth 1) phase: Newly formed cell increases
in size. Protein synthesis is very active. Cell undergoes
differentiation and performs its function. At the end of G1,
the cell checks whether it is ready for division
• Some cells in G1 enter the Go phase (quiescent).
Permanent and stable cells are in Go. Stable cells can
reenter the cell cycle on appropriate stimulation.
• S phase: Phase of DNA synthesis/ DNA replication.
Enzymes of replication are most active. The entire
chromosome replicates and at the end of S phase, the
chromatid number doubles. Each chromosome has two
sister chromatids
• G2 phase: The chromatid number is double. The cell size
increases to help the formation of two new daughter cells.
The entire genome is scanned for any mistakes during
replication. Post-replication DNA repair mechanisms are
active during this stage
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Stages of cell cycle

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Cell cycle control

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Cell cycle control
• G1→S phase & G2→M
phase are important
check points in a cell
cycle
• p53 & Rb proteins are
important at the G1→S
checkpoint
• Cyclins regulate the
entry of cells into
various phases of the
cell cycle
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 Cell cycle control
• Growth factors stimulate cell division. Growth factors
serve as signals that tell the cell to move through the cell
cycle in order to divide.
• Severe defects in chromosomes block progression
through the cell cycle, and can lead to cell suicide, or
apoptosis. Proteins (p53, Rb – tumor suppressor
genes) checks for DNA damage before cell exits the G1
phase
• In addition, cells have a finite lifespan, and at some
point are no longer able to divide.
• Cancers are diseases in which there is a defect in the
regulation of the cell cycle. Cancer cells are rapidly
dividing cells that are no longer controlled
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Role of p53 in
the cell cycle

‘Molecular policeman’
‘Guardian of the genome’

-p53 exists in non-stressed cells at a very low concentration.

-Under stress conditions, the p53 protein accumulates and induces the
transcription of various genes involved in cell-cycle control, apoptosis, DNA
repair, differentiation and senescence.
-The loss of p53 tumor-suppressor activity allows the proliferation of the cells
that are damaged under the stress conditions. This uncontrolled proliferation
can lead to tumor development.
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 Mitosis
• The chromatid number is doubled at the
end of interphase (G2) – remember replication
takes place in S phase – each chromosome contains 2
sister chromatids
• During mitosis, there is segregation of the
sister chromatids and later cytoplasmic
division to form two daughter cells
• The genetic composition of the daughter
cells is identical to that of the parent cell
• Takes place during growth of the embryo
and in all somatic cells capable of cell
division 13
 Stages of Mitosis
• Prophase: Nuclear
envelope dissolves.
Mitotic spindle forms.
Chromosomes start
condensing and become
visible. Chromosomes Prophase

start binding to the

spindle

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 Stages of Mitosis
• Metaphase: Chromosomes
condense and are maximally
visible. Chromosomes align at
the equator. Time at which they
are visualized by karyotyping.
The microtubules attach to the Metaphase
centromere kinetochores during
cell division
• Anaphase: Sister chromatids
move to the centrioles.
Separation of the sister Anaphase
chromatids 15
Sister chromatids
 Stages of Mitosis
• Telophase: Sister chromatids
move to opposite poles. Nuclear
envelope starts forming.
Chromosomes become less
condensed. Division of the cell
to form two new daughter cells Telophase
(cytokinesis)
• The daughter cells have the
same genetic composition as
the parent cell (2n)

Cytokinesis
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Phase of Events taking place
cell cycle
G1

Go

G2

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 You are observing a cell culture. Growth
factors are added to the medium and cells
transition from G1 to S phase. At the end of
S phase, you observe that there are

A. 23 chromosomes & 23 chromatids

B. 46 chromosomes & 92 chromatids
C. 46 chromosomes & 46 chromatids
D. 92 chromosomes & 92 chromatids
E. 23 chromosomes & 92 chromatids

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 G0 occurs in non-dividing
M phase includes mitosis and cytokinesis cells, it is an active process,
not just a stall in G1.
Occurs in cells that have
G2 = one large cell with terminally differentiated
TWO SISTER into tissue cells, eg
CHROMATIDS PER Neurons. ONE CHROMATID
CHROMOSOME . Cell is PER CHROMOSOME.
ready for division

G1 = is the most variable in

length, differences in rates of
division are primarily a
result of differences in G1
length. DNA in the cell is in
a DIPLOID (two copies of
S phase: DNA synthesis occurs, each chromosome, mom+dad copies)
chromatids are copied and joined at ONE CHROMATID PER
centromere. TWO SISTER CHROMOSOME.
CHROMATIDS PER CHROMOSOME.
 Meiosis
• Takes place only in the gamete forming
cells of ovary or testis (germline cells), final
stages of gametogenesis
• The gametes formed are haploid (n)
• Each gamete is genetically unique
• Meiosis results in the formation of four
gametes, each of which has only 23
chromosomes: one of each kind of
autosome and either an X or a Y (23X or
23Y in males, 23X in females).
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 Meiosis
• Each chromosome is duplicated before meiosis
to form two sister chromatids
• Homologous chromosomes undergo exchange
of short fragments of their genetic material –
homologous recombination
• Homologous recombination is responsible for
the genetic variation between the gametes. Each
gamete is genetically unique
• Meiosis occurs in two stages:
– Meiosis I: Homologous chromosomes separate
– Meiosis II: Sister chromatids of a chromosome
separate
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 Meiosis II
Meiosis I

23,Y

23,Y

23,X
Meiotic
crossover- Homologous
homologous chromosomes 23,X
46,XY
recombination separate Sister Each gamete has a
http://highered.mcgraw- chromatids unique genetic
hill.com/sites/0072495855/student_view0/chapte separate composition & is
r28/animation__how_meiosis_works.html
haploid 22
http://www.youtube.com/watch?v=iCL6d0OwKt8
Meiosis II

1P

Duplication of the
chromosome to
Meiosis I
1P 1P
form two sister
chromatids 1M

1M
1P

1P

1P

Meiotic 1M
crossover- 1M 1M
homologous
recombination

Homologous Sister
chromosomes chromatids
separate separate
1M
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 Crucial roles of meiosis
• Formation of a haploid gamete (n). (After
fertilization, the diploid set of chromosomes
is present in the zygote)
• Meiosis allows for genetic recombination
and genetic diversity (the gametes formed
from an individual are not alike)

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 Nondisjunction

Responsible for trisomy after fertilization

Nondisjunction during meiosis I: Nondisjunction during meiosis II:

Homologous chromosomes do Sister chromatids of a
NOT separate chromosome do NOT separate

What is the chromosome number in the encircled gametes?

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Meiotic I nondisjunction in males
Meiosis II No sex
Meiosis I chromosome
but all the
nondisjunction autosomes
No sex
chromosome
Duplication of the but all the
chromosome to autosomes

form two sister No sex

chromatids chromosome
X but all the
Y autosomes

XY
Meiotic
crossover-
homologous
recombination
XY
Homologous Sister
chromosomes chromatids
do NOT separate 26
separate
 Ovum Fertilization

Sperm cells
Turner syndrome,
1 and 2
45,X

Sperm cells Klinefelter

3 and 4 syndrome, 47,XXY
XXY

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Meiotic II nondisjunction in males Meiosis II
No sex
nondisjunction chromosome
but all the
autosomes

Duplication of the
chromosome to
Meiosis I
form two sister
chromatids
X Sister
Y
chromatids
YY
do NOT
separate
No sex
chromosome
Meiotic but all the
autosomes
crossover-
homologous
recombination

Homologous Sister
chromatids XX
chromosomes
separate do NOT 28
separate
 Gamete Formation in Humans
Overall gametogenesis is the same in males and females but there are some very
significant differences
Male meiosis
produces four
sperm cells per
round.
Female meiosis
produces one
egg and three
polar bodies.
Mitotic division of
cells occur at
different times in
males and
females.
Females have
undergone all
mitotic division
by birth.
 females Meiosis

Oogenesis begins
during prenatal
development

Primary oocytes (several

million) arrest at prophase-I
of meiosis during fetal
development Meiosis is
Most degenerate, and
completed only
about 400 remain to mature after fertilization
and ovulate

Ovulation, on average once

per month (arrest at 30
prophase-I)
 Differences between gametogenesis in males & females

Males Females
Commences puberty early embryonic life (Oocytes are arrested
in prophase-I of meiosis until ovulation)
# of mitoses in 30-500 20-30
gamete
formation
gamete 4 spermatids 1 ovum, 3 polar bodies
production per
meiosis
gamete 100-200 1 ovum per menstrual cycle
production million per
ejaculate

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What are the defects if maternal or paternal age is
increased??
• There is a higher risk of non-disjunction (non
separation of the homologous chromosomes/
sister chromatids) in the meiotic divisions in a
female greater than 35 years, resulting in a
higher risk of trisomy (chromosomal
abnormality) in the fetus
• Higher the paternal age, greater is the risk of
development of new dominant single gene
mutations (errors during replication)

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 Differences between mitosis and meiosis
Mitosis Meiosis
• Takes place in all • Takes place only in
dividing somatic cells, germline cells during
& during gametogenesis
embryogenesis & • The gametes formed
initial stages of have a unique genetic
gametogenesis composition due to
• The genetic meiotic crossover
composition of the (homologous
daughter cells is recombination)
same as the parent • The gametes are
(46,XX or 46,XY) haploid (23,X or 23,Y)
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 You are observing mitotic divisions and
meiotic divisions. Which of the following is a
feature of meiosis?

A. The chromosome number remains the same

B. The chromosome number doubles
C. The chromosome number becomes haploid
D. There is no exchange of genetic material
between homologous chromosomes

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 A cell division in humans is observed. Cells in
culture have their 23 total chromosomes (each
composed of two sister chromatids) arranged
along the equator of the cell. Which phase of the
cell cycle is being observed?
A. Prophase of mitosis
B. Metaphase of mitosis
C. Anaphase of mitosis
D. Prophase I of meiosis
E. Metaphase I of meiosis
F. Metaphase II of meiosis
G. Anaphase II of meiosis
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• At the beginning of meiosis, there are
____ chromosomes & _____ sister
chromatids
• At the end of meiosis I, each cell has
_____ chromosomes & ______ sister
chromatids (reduction division)
• At the end of Meiosis II, there are _____
chromosomes & ______ chromatids

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• At the beginning of meiosis, there are 46
chromosomes & 92 sister chromatids
• At the end of meiosis I, each cell has 23
chromosomes & 46 sister chromatids
(reduction division)
• At the end of Meiosis II, there are 23
chromosomes & 23 chromatids

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