Cell Cycle

&
Cell Division

LS1001

Prof. Surajit Das

 The cell cycle
• The eukaryotic cell cycle consists
of distinct phases
• The most dramatic events are
nuclear division (mitosis) and
cytoplasmic division (cytokinesis)
• This is the M phase
• The rest of the cell cycle is called
interphase which is, deceptively,
uneventful
• During interphase the cell
replicates its DNA, transcribes
genes, synthesises proteins and
grows in mass
 Phases of the cell cycle

– Gap 1 (G1): cell growth and

normal functions
– DNA synthesis (S): copies
DNA
– Gap 2 (G2): additional
growth (chromatids become
replicated chromosomes)
– Mitosis (M): includes
division of the cell nucleus
(mitosis) and division of the
cell cytoplasm (cytokinesis)

• Mitosis occurs only if the cell is large enough and the DNA
undamaged.
 Interphase
• Cells spend the majority of their cell cycle in interphase.
• The purpose of interphase is for cell growth.
• By the end of interphase a cell has two full sets of DNA
(chromosomes) and is large enough to begin the division
process.

• G1 - Cells undergo majority of growth

• S - Each chromosome replicates (Synthesizes) to produce sister
chromatids
– Attached at centromere
– Contains attachment site (kinetochore)
• G2 - Chromosomes condense - Assemble machinery for division
such as centrioles
 Cell cycle control
• Cell cycle machinery is subordinate to a cell cycle control
system
• The control system consists mainly of protein complexes
• These complexes consist of a cyclin subunit and a Cdk
(cyclin dependent kinase) subunit
• The cyclin has regulatory function, the Cdk catalytic
function
• Cdk expression is constant, but cyclin concentrations
rise and fall at specific times in the cell cycle
• The Cdks are cyclically activated by cyclin binding and by
phosphorylation status
• Once activated, Cdks phosphorylate key proteins in the
cell
• Different cyclin-Cdk complexes trigger different cell cycle steps
• Some drive the cell into M phase, others into S phase
• The cell cycle control system has in-built molecular breaks
(checkpoints)
• These checkpoints ensure that the next step does not begin until
the previous one is complete
• MPF (“maturation-promoting factor” or “M-phase-promoting-
factor”) triggers the cell’s passage past the G2 checkpoint to the M
phase.
• MPF promotes mitosis by phosphorylating a variety of other
protein kinases.
 Three checkpoints
I) G1/S cell cycle checkpoint
II) G2/M DNA damage checkpoint
III) Mitosis checkpoint

G1/S cell cycle checkpoint

controls the passage of eukaryotic cells from the first

'gap' phase (G1) into the DNA synthesis phase (S).

Checks:
That the size is CORRECT
That the environment is CORRECT
 G1/S cell cycle checkpoint
How do they do that?
Major proteins involved:
Cyclins (proteins) - level fluctuate in the cell cycle.
&
Cyclin dependent KINASES* (Cdks)
They add phosphate groups to proteins that control processes in
the cell cycle.
They only do this when the cyclins are present.
 G2/M DNA damage checkpoint
•The G2/M DNA damage checkpoint prevents the
cell from entering mitosis (M phase) if the genome is
damaged.
•It also checks if the cell is big enough (i.e. has the
resources to undergo mitosis)
•Almost exclusively, internally controlled

M checkpoint
• The M checkpoint is where the attachment of the
spindle fibres to the centromeres is assessed.
• Only if this is correct mitosis can proceed.
• Failure to attach spindle fibres correctly would lead
to failure to separate chromosomes
 Cell division
• The continuity of life from one cell to
another is based on the reproduction of
cells via cell division.

• This division process occurs as part of the

cell cycle (the life of a cell from its origin in
the division of a parent cell until its own
division into two).

• The division of a unicellular organism (e.g.

Amoeba) reproduces an entire organism,
increasing the population.

• Cell division is also central to the

development of a multicellular organism
that begins as a fertilized egg or zygote.
 Cell division distributes identical sets of chromosomes to daughter cells

• A cell’s genetic information (genome ) is packaged as DNA.

• In prokaryotes, the genome is often a single DNA molecule.
– In eukaryotes, the genome consists of several DNA molecules.
• A human cell must duplicate about 3 m of DNA and separate the
two copies such that each daughter cell ends up with a complete
genome.
• DNA molecules are packaged into chromosomes.
– Every eukaryotic species has a characteristic number of chromosomes in the
nucleus.
– Human somatic cells (body cells) have 46 chromosomes.
– Human gametes (sperm or eggs) have 23 chromosomes, half the number in
a somatic cell.
• Each eukaryotic chromosome consists of a long, linear DNA
molecule.
 Prokaryotic Chromosome
The DNA of
prokaryotes
(bacteria) is one,
circular
chromosome
attached to the
inside of the cell
membrane
 Eukaryotic Chromosomes
 All eukaryotic cells store genetic
information in chromosomes
 Most eukaryotes have between 10 and
50 chromosomes in their body cells
 Human body cells have 46 chromosomes
or 23 identical pairs
 Chromosomes in Dividing Cells

Duplicated
chromosomes are
called chromatids
& are held
together by the
centromere

Called Sister Chromatids

15
MITOSIS
 Mitosis
 Some haploid & diploid cells divide by mitosis.
 Each new cell receives one copy of every
chromosome that was present in the original cell.
 Produces 2 new cells that are both genetically
identical to the original cell.

DNA duplication
during interphase

Mitosis

Diploid Cell
 What Occurs Before Mitosis?
• Mitosis is a type of cell division that involves the
production of two daughter cells that have the
same genetic makeup like the parent cell.

•Before the actual mitosis, the cell is prepared to make sure

it is ready to undergo the process.

*For instance, the cell undergoes a process called the

interphase as the preparatory phase before mitosis.
Interphase is divided into three major stages: G1, S, and G2
phase.

*During the S phase of interphase, the chromosomes are

duplicated in order to make sure that each daughter cell will
receive one copy of every chromosome.
Cell Cycle and Check Points
Mitosis can be divided into stages

• Interphase
• Prophase
• Metaphase
• Anaphase
• Telophase & Cytokinesis
Overview of Cell Division
 Mitotic Division of an Animal Cell

G2 OF INTERPHASE PROPHASE PROMETAPHASE

Centrosomes Aster Fragments
(with centriole pairs) Chromatin Early mitotic Kinetochore
spindle Centromere of nuclear
(duplicated) Nonkinetochore
envelope
microtubules

Nucleolus Nuclear Plasma Chromosome, consisting Kinetochore

envelope membrane of two sister chromatids microtubule
 Mitotic Division of an Animal Cell

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Metaphase
plate Cleavage Nucleolus
furrow forming

Nuclear
envelope
Spindle Centrosome at Daughter forming
one spindle pole chromosomes
G2 of Interphase
• A nuclear envelope bounds the nucleus.
• The nucleus contains one or more nucleoli (singular,
nucleolus).
• Two centrosomes have formed by replication of a
single centrosome.
• centrosome is an organelle that is the main place
G2 OF INTERPHASE
where cell microtubules are organized.
Centrosomes
• In animal cells, each centrosome features two (with centriole pairs) Chromatin
centrioles. (duplicated)

• Chromosomes duplicated during S phase

Nucleolus Nuclear Plasma

envelope membrane
Prophase
• The chromatin fibers become
more tightly coiled, condensing
into discrete chromosomes.
• The nucleoli disappear.
• Each duplicated chromosome
appears as two identical sister
chromatids joined together.
• The mitotic spindle begins to form. PROPHASE
• It is composed of the centrosomes Aster
Early mitotic
and the microtubules that extend spindle Centromere
from them.
• The radial arrays of shorter
microtubules that extend from the
centrosomes are called asters
(“stars”).
• The centrosomes move away from
each other, apparently propelled by
the lengthening microtubules Chromosome, consisting
between them. of two sister chromatids
Chromosome condensation

During
Prophase, the
chromatin
condenses into
rod shaped
structures called
chromosomes.
 Chromosome Duplication
• Because of duplication, each condensed chromosome
consists of 2 identical chromatids joined by a centromere.
• Each duplicated chromosome contains 2 identical DNA
molecules (unless a mutation occurred), one in each
chromatid:

Non-sister
chromatids

Centromere Duplication

Sister Sister
chromatids chromatids
Two unduplicated
chromosomes Two duplicated chromosomes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or isplay.
Metaphase
• Metaphase is the longest stage of
mitosis, lasting about 20 minutes.
• The centrosomes are now at opposite
ends of the cell.
•The chromosomes convene on the
metaphase plate, an imaginary plane METAPHASE
that is equidistant between the spindle’s Metaphase
plate
two poles.
•The chromosomes’ centromeres lie on
the metaphase plate.
• For each chromosome, the
kinetochores of the sister chromatids are
attached to kinetochore microtubules
coming from opposite poles.
Spindle Centrosome at
• The entire apparatus of microtubules is one spindle pole
called the spindle because of its shape.
Anaphase
• Anaphase is the shortest stage of mitosis,
lasting only a few minutes.
• Anaphase begins when the two sister
chromatids of each pair suddenly part.
• Each chromatid thus becomes a full-
fledged chromosome.
• The two liberated chromosomes begin ANAPHASE

moving toward opposite ends of the cell,

as their kinetochore microtubules
shorten. Because these microtubules are
attached at the centromere region, the
chromosomes move centromere first (at
about 1 µm/min).
• The cell elongates as the
nonkinetochore microtubules lengthen.
• By the end of anaphase, the two ends of Daughter
chromosomes
the cell have equivalent—and
complete—collections of chromosomes.
Separation of Sister Chromatids
Telophase
• Two daughter nuclei begin to
form in the cell.
• Nuclear envelopes arise from
the fragments of the parent
cell’s nuclear envelope and TELOPHASE AND CYTOKINESIS
other portions of the
Cleavage Nucleolus
endomembrane system. furrow forming
• The chromosomes become
less condensed.
• Mitosis, the division of one
nucleus into two genetically
identical nuclei, is now Nuclear
envelope
complete. forming
Phase of Mitosis
 Cytokinesis
•Cytokinesis is the division of the
cytoplasm into two individual cells.

•The process of cytokinesis

differs somewhat in plant and
animal cells.

•In animal cells, the cell

membrane forms a cleavage
furrow that eventually pinches
the cell into two nearly equal
parts, each part containing its
own nucleus and cytoplasmic
organelles.
The typical animal life cycle
 MEIOSIS
Reduces chromosome number
from diploid to haploid

Meiosis reduces chromosome number by

copying the chromosomes once, but dividing
twice.
The first division (meiosis I) separates
homologous chromosomes.

The second (meiosis II) separates sister

chromatids.
 Meiosis
• The form of cell division by which gametes
(sperm or egg), with half the number of
chromosomes, are produced.
• Diploid (2n)  haploid (n)
• Gametes have half the # of chromosomes
• Occurs only in gonads (testes or ovaries)
Male : spermatogenesis
Female: oogenesis
• Meiosis is sexual reproduction.

• Two divisions (meiosis I and meiosis II).

Spermatogenesis
n=23
human
sex cell
sperm
n=23
n=23

2n=46
haploid (n)
n=23
diploid (2n) n=23

n=23

meiosis I meiosis II
 Interphase I

• Similar to mitosis interphase.

• Chromosomes replicate (S phase).

• Each duplicated chromosome consist of two

identical sister chromatids attached at their
centromeres.

• Centriole pairs also replicate.

 Meiosis I (four phases)
• Cell division that reduces the chromosome
number by one-half.

• four phases:
a. prophase I
b. metaphase I
c. anaphase I
d. telophase I
 Prophase I
• Longest and most complex phase.

• Chromosomes condense.

• Synapsis occurs: homologous chromosomes come together to

form a tetrad.

• Tetrad is two chromosomes or four chromatids (sister and nonsister

chromatids).

Homologous chromosomes

sister chromatids Tetrad sister chromatids

 Crossing Over
• Crossing over (variation) may occur between nonsister
chromatids at the chiasmata.
• Crossing over: segments of nonsister chromatids break and
reattach to the other chromatid.
• Chiasmata (chiasma) are the sites of crossing over.
Tetrad
nonsister chromatids

chiasmata: site of
crossing over
 Prophase I
spindle fiber centrioles

aster
fibers
 Metaphase I
• Shortest phase
• Tetrads align on the metaphase plate.
• INDEPENDENT ASSORTMENT OCCURS:
1. Orientation of homologous pair to poles is random.
2. Variation
3. Formula: 2n
Example: 2n = 4
then n = 2
thus 22 = 4 combinations
 Question:
• In terms of Independent Assortment -
how many different combinations of
sperm could a human male produce?
 Answer
• Formula: 2n
• Human chromosomes: 2n = 46
n = 23

• 223 = ~8 million combinations

 Anaphase I
• Homologous chromosomes separate and
move towards the poles.

• Sister chromatids remain attached at their

centromeres.
 Telophase I
• Each pole now has haploid set of
chromosomes.

• Cytokinesis occurs and two haploid daughter

cells are formed.
Telophase I
Summary of Meiosis I
 Meiosis II
• No interphase II
(or very short - no more DNA replication)

• Remember: Meiosis II is similar to mitosis

 Prophase II
• same as prophase in mitosis
 Metaphase II
• same as metaphase in mitosis

metaphase plate metaphase plate

 Anaphase II
• same as anaphase in mitosis
• sister chromatids separate
 Telophase II
• Same as telophase in mitosis.
• Nuclei form.
• Cytokinesis occurs.

• Remember: four haploid daughter cells

produced.

gametes = sperm or egg

Telophase II
 Meiosis- Summary
n=2

sex cell sperm

n=2
n=2

2n=4
haploid (n)
n=2
diploid (2n) n=2

n=2

meiosis I meiosis II
Comparison between Mitosis and meiosis
 Summary

• Mitosis produces two identical daughter cells, but meiosis produces 4 very different cells.