Cell cycle and mitosis

Dr Roberts
Learning outcomes
1. Describe the stages of the cell cycle
2. Explain the process of DNA replication
3. Explain the process of cytokinesis
4. Describe the signals which induce somatic cell division
Cell division
• The cell cycle is the orderly sequence of events required
for the duplication of a eukaryotic cell into two
genetically identical daughter cells.
• The cell undergoes nuclear division (karyokinesis, a stage
of mitosis) and cytoplasmic division (cytokinesis)
• Is required: to replace dead/injured cells from wear &
tear, stress, chemical damage etc
• And adds new ones in tissue growth
• A human being goes from 1 cell to around 37 trillion

Do all body (somatic) cells undergo division?

Apoptosis and necrosis

•Cells have a finite

number of divisions
•Controlled by activation
of ‘suicide genes’
•bcl-2 prevents apoptosis
unless disrupted
•Between 50 and 70
billion cells die each day
due to apoptosis in the
average human adult
 Cell cycle
Just checking… what are:
• Cells must first replicate
Genes
all their homologous
Chromosomes
chromosomes
DNA
• Cell replication has 2
main stages
• Interphase (when the
cell is not dividing)
• The mitotic (M) phase
when a cell is dividing
Interphase
• It is the phase between two successive mitotic divisions
• During this phase the cell grows and prepares itself for
division
• It may be subdivided into
– G1 phase
– S phase and
– G2 phase

•Most cells only spend a small amount of time dividing

•During interphase cells are carrying out normal functions &
preparing to divide if needs be
•An interphase cell in G0 is not dividing or preparing to divide
e.g. most muscle cells and neurones
•Cells do not pass G0 (normally) without a growth promoting
signal
 G1 phase
• Cells don’t pass G1 without growth factors
• Lasts for about 8-10 hours of a 24 hour cycle
(can last weeks)
• High rate of metabolism
• Protein synthesis
• Vigorous growth
• Duplicates most organelles
• Centrosome replication begins
 • Lasts for about 8 hours
S phase • DNA replicates.
• Synthesis of new histones.
• Assembly of new chromatin.
DNA replication
• It is catalysed by enzyme DNA polymerase.
• Energy for the process comes from hydrolysis of ATP.
• The DNA uncoils due to breaking of hydrogen bonds between
nitrogen bases
• The original strands function as templates for the synthesis of
new strands.
• Each new strand contains bases complementary to the original
strand.
• Hydrogen bonds are formed between the bases of the original
and the new strands creating two daughter molecules
• The method is termed as semi conservative as each daughter
molecule contains only one newly produced strand
 G2 phase
• It lasts for 4-6 hours
• Synthesis of enzymes and proteins essential for cell
division
• Organelle replication is completed
• Replication of centrioles completed (form the spindle
apparatus associated with the movement of DNA)
Mitotic phase
• It includes
– Karyokinesis: Division of nucleus and
– Cytokinesis: Division of cytoplasm
• It is a continuous process but for the sake of
convenience is described in four phases.
– Prophase
– Metaphase
– Anaphase and
– Telophase
• (Lasts for an hour or less in human cells)
Mitosis
Prophase
• It is longest sub phase of mitosis.
Early prophase:
• chromatin coils and condense into bar like chromosomes
• Each chromosome consists of 2 identical threads
(chromatids) held together at a point called centromere.
• Nucleoli disappear
• Cytoskeletal microtubules disassemble
• Centriole pairs separate and move towards opposite ends
due to growth of new microtubules forming the mitotic
spindle
Prophase
• Condensing chromosome
material stops them tangling
during mitosis
• Each chromosome is now
made of 2 chromatids
• Kinetochore needed for spindle
attachment
• Growing spindle pushed
centrosomes to opposite poles
• Is required to separate
chromatids
Metaphase
• Chromosomes undergo maximum coiling
• Chromosomes arrange themselves along the
middle of the cell with the centromeres aligned
at the equator of the spindle (metaphase plate)
Anaphase
• The kinetochore of each chromatid splits
• The separated chromatids are now termed as daughter
chromosomes.
• They move towards opposite poles due to the interactions
between the kinetochore and microtubules.
Telophase
• Begins after the chromosomal movement stops and the
identical sets of chromosomes are at the opposite poles.
• Chromosomes start uncoiling and transform into chromatin
• Nuclear envelope reforms around the chromatin mass
• Nucleoli reappear and mitotic spindle disappears.
• This marks the end of karyokinesis
 Cell cycle and mitosis
Dr Roberts
Learning outcomes
1. Describe the stages of the cell cycle
2. Explain the process of DNA replication
3. Explain the process of cytokinesis
4. Describe the signals which induce somatic cell division
Cytokinesis
• It begins during late anaphase and continues through telophase
and beyond.
• In case of animal cells, the cell organelles such as ribosomes
and mitochondria become evenly distributed around the two
daughter nuclei

•The cytoplasm develops a

cleavage furrow that deepens,
finally separating the two
daughter cells, each with the
same complement of
chromosomes as the parent
cell.
 Key terms
• Centrosome: an organelle that
serves as the main microtubule
organizing centre of the animal cell
as well as a regulator of cell-cycle
progression
• Kinetochore: the protein structure
on chromatids where the spindle
fibres attach during cell division to
pull sister chromatids apart
• Centromere: part of a chromosome
that links sister chromatids. During
mitosis, spindle fibers attach to the
centromere via the kinetochore
1 2 3 4 5
 Just checking…
1. How are G1 and G2 different?
2. What is the main feature of anaphase?
3. What are chromatids and where do they
come from?
4. Why is the kinetochore important for cell
division?
5. How does the contractile ring form?
 Cell cycle and mitosis
Dr Roberts
Learning outcomes
1. Describe the stages of the cell cycle
2. Explain the process of DNA replication
3. Explain the process of cytokinesis
4. Describe the signals which induce somatic cell division
 Control of cell destiny
Cell destiny

G0: To remain alive To grow and divide

and functioning Cell death (apoptosis)
without dividing
•The signals regulating these processes are an intense area of research
•Cyclin dependent kinases (Cdk’s) regulate the initiation of cell growth
•They are switched on and off by cyclins (their levels rise & fall in the
cell cycle)

•Extracellular compounds are the key regulators of these processes

 Cell growth
• To move through the cell cycle cells need a mitogenic signal
• These are normally induced by proteins or large peptides (a
growth factor (GF))
• They are often produced by cells neighbouring a cell that
just dies
• The GF binds to a receptor on the cell surface and activates
a signalling cascade
• Contact inhibition can blunt this
• Many cells also have anchorage dependence (they can only
divide when attached to the ECM)
 Cell cycle checkpoints
• Cell cycle checkpoints are control mechanisms that
ensure the reliability of cell division
• These checkpoints verify whether the processes at
each phase of the cell cycle have been accurately
completed before progression into the next phase.
• checkpoints assess DNA damage, which is detected by
sensor mechanisms.
• When damage is found, the checkpoint uses a signal
mechanism either to stall the cell cycle until repairs
are made or, if repairs cannot be made, to target the
cell for destruction via apoptosis
 Cell cycle checkpoints
• There is a phase late in G1 phase called the restriction
point (RP, or the restriction checkpoint); cells that
should cease division exit the cell cycle and enter G0.
• Cells that continually divide in the adult human
include hematopoietic stem cells and gut epithelial
cells. Their re-entrant into the cell cycle is possible
only by overcoming the RP.
• This is achieved by growth factor-induced expression
of cyclin D proteins. These then overcome the G0
barrier and are able to enter the cell cycle
 Cell cycle checkpoints
• In growth hormone-induced or oncogenic-induced progression,
cyclin D expression increases. Increased expression of cyclin D
allows its interaction with CDK4.
• Once active CDK4-cyclin D complexes form, they phosphorylate
the tumor suppressor (growth inhibitor) retinoblastoma protein
(Rb), which relieves the inhibition of the transcription factor E2F.
• E2F is then able to cause expression of proteins needed for cell
growth eg cyclin E.
 Checkpoints
• The second checkpoint is located at the end of G2
phase, triggering the start of the M phase
• The mitotic spindle checkpoint occurs at the point
in metaphase where all the chromosomes should
have aligned at the mitotic plate and be under
bipolar tension.
• The tension created by this bipolar attachment is
sensed, which initiates the anaphase entry
1. What is a check point?
2. When do the check points occur
3. How do cyclins regulate the cell cycle?
Cancer and the cell cycle
Mitotic Inhibitors
• Often plant-derived
• Affect microtubules the M phase of the cell cycle
• used to treat tumours inc. breast, lung, myelomas,
lymphomas, and leukaemia's.
• e.g. the taxanes (paclitaxel, docetaxel) & vinca alkaloids