What is the cell cycle?

• The cell cycle is a regular series of

events that cells go through as they
grow and divide.
• The cell cycle for prokaryotic cells is a
quick succession of growth, DNA
replication, and cell division. Cell
division in prokaryotes is a one-step
process called binary fission (shown
right).
• Eukaryotic cells have a more complex
cell cycle than prokaryotic cells.
 How is the eukaryotic
cell cycle divided?
• The time between cell divisions is
called interphase. The length of
interphase varies depending on cell
type.
• Eukaryotic interphase is divided into
three steps, or phases: G1, S, and G2.
• Eukaryotic cells divide during the M
phase of the cell cycle. The M phase
consists of two steps: mitosis and
cytokinesis.
 What happens during each phase of
eukaryotic interphase?
• G1: Cells do most of their growing
during this phase. It begins when
mitosis is complete and ends when
DNA replication begins.
• S: DNA is synthesized as
chromosomes are replicated.
• G2: Many of the molecules and cell
During interphase, the
structures required for cell division cell grows and
replicates its DNA.
are produced; usually the shortest
phase of the cell cycle.
 What happens during the M phase
of the eukaryotic cell cycle?
• The M phase is usually much
shorter than interphase and
results in two daughter cells.
• The first step of the M phase is
mitosis. The cell’s nucleus
divides during mitosis.
• The second step of the M
phase is cytokinesis, during
which the cell’s cytoplasm is
divided.
What are the steps
of mitosis?
• Mitosis consists of four steps:
prophase, metaphase,
anaphase, and telophase.
• Prophase: nuclear envelope
breaks down, DNA condenses,
spindle begins to form.
• Metaphase: replicated
chromosomes, which appear as
paired sister chromatids, line
up across the center of the cell
and attach to spindle.

(contd.)
What are the steps of
mitosis?
• Anaphase: sister chromatids
separate and move toward
ends of the cell.
• Telophase: chromosomes
disperse, nuclear envelope
reforms.
 What completes the M phase
of the cell cycle?
• Cytokinesis completes the M phase of
the cell cycle. It may begin while
telophase is still taking place.
• During cytokinesis, the cytoplasm
(which includes all of the contents of a
eukaryotic cell outside the nucleus)
draws inward, eventually pinching off
into two nearly equal parts. Each part
contains a nucleus.

(contd.)
 What completes the M phase
of the cell cycle?

• In plant cells and other

eukaryotic cells that have a cell
wall, a cell plate forms halfway
between the divided nuclei. It
gradually develops into cell
membranes and forms a
complete cell wall surrounding
each daughter cell.
• Upon the completion of
cytokinesis and the M phase, a
cell enters interphase.
 When does DNA replicate?
• Before a cell divides in the M
phase, its DNA is duplicated by a
process called DNA replication.
• DNA replication occurs at the
beginning of the S phase of
interphase.
• It ensures that each daughter cell
that results from cell division will
have a complete set of DNA
molecules.
DNA replication

6.6.Review
Review Why
Whydoes
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DNA
replicate before cell division?
replicate before cell division?
 How is the cell cycle controlled?
• Movement through the cell cycle
is subject to control by internal
and external regulators.
• Internal regulators ensure that a
cell does not move from one 8.8.Infer
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from
phase to another until certain entering
entering anaphase until allofofits
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chromosomes are attached tothe
are attached to the
• External regulators respond to mitotic spindle. Are these
mitotic spindle. Are these
regulatory
regulatoryproteins
proteinsinternal
internal
events outside the cell and regulators
regulatorsororexternal
externalregulators?
regulators?
direct cells to either speed up or
slow down the cell cycle.
Progression of the cell cycle is regulated by feedback
from intracellular events
• Cyclin-Dependent Protein Kinase (Cdks)
A Cdks is an enzyme that adds negatively charged
phosphate groups to other molecules in a
process called phosphorylation.
Through phosphorylation, Cdks signal the cell
that it is ready to pass into the next stage of
the cell cycle. Cyclin-Dependent Protein
Kinases are dependent on cyclins, another class
of regulatory proteins. Cyclins bind to Cdks,
activating the Cdks to phosphorylate other
molecules.
Cyclins are named such because they undergo a
constant cycle of synthesis and degradation during
cell division.
When cyclins are synthesized, they act as an
activating protein and bind to Cdks forming a
cyclin-Cdk complex. This complex then acts as a
signal to the cell to pass to the next cell cycle
phase. Eventually, the cyclin degrades, deactivating
the Cdk, thus signaling exit from a particular phase.
Checkpoints ensure the cell cycle proceeds
without errors
 Checkpoint: spindle assembly
• Mitosis must not complete unless all the
chromosomes are attached to the mitotic spindle
• Mitotic checkpoint delays metaphase to
anaphase transition until all chromosomes are
attached
• Prolonged activation of the checkpoint -->cell
death
• Mechanism of many anti-cancer drugs
 Cells can withdraw from the cell cycle and
dismantle the regulatory machinery

• G0 is a quiescent state

• Cdks and cyclins disappear

• Some cells enter G0 temporarily and

divide infrequenty (I.e. hepatocytes)

• Other differentiated cell types

(neurons) spend their life in G0
What role does the cell cycle have in
the growth of organisms?
• As an organism grows, its cells cannot simply get larger and larger.
The reason is that as cells get bigger, their surface area to volume
ratio decreases.
• If a cell gets too big, its surface area is not large enough to get
adequate oxygen and nutrients in and waste out through the cell
membrane.
• Cells must divide to accommodate the needs of a growing
organism.
 Why does the rate of the cell cycle
vary among cell types?
• Cells types lost or damaged to wear and tear move quickly
through the cell cycle to provide replacements.
• In adults, cells in skin and the digestive tract move through
the cell cycle very quickly; cells in the nervous system divide
very rarely.
• During embryonic development, cells progress through the
cell cycle very quickly, often dividing as frequently as every
hour or two.

(contd.)
 Why does the rate of the cell cycle
vary among cell types?
• Upon injury, cells often speed up their
passage through the cell cycle to aid in
healing. The timing of the cell cycle returns
to normal once the injury heals.

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• Mechanism of cell cycle regulation molecules revealed
• The new research shows how a large molecule known as the anaphase-
promoting complex/cyclosome (APC/C) regulates cell division by marking
proteins within cells for destruction.
• Cancer is a disease of cell proliferation, which occurs through the biological
process known as the cell cycle. A series of checks and controls regulate
each stage of this complex process, but in cancer these 'brakes' become
faulty.
• The APC/C is one of those cell cycle controls. By marking a set of proteins for
destruction, it releases the brakes and allows cell division to proceed.
• Until recently nobody was quite sure how the APC/C worked at the
molecular level, but a team of scientists at the Institute of Cancer Research
(ICR) have now uncovered how this molecular targeting system works.
• Study leader Professor David Barford FRS, Professor of Molecular Biology at
the ICR, said: "We have described how proteins marked for destruction are
recognised by cell cycle regulatory systems. We hope that this information
will allow us to begin developing therapies that control APC/C activity in
cancer."
• APC/C marks proteins for destruction by 'tagging' them with a small protein label
called 'ubiquitin'. These tags are recognised by molecular machines known as
proteasomes, which are then responsible for breaking down the marked proteins.
• The role of the APC/C is to ensure that the correct proteins are destroyed at the right
time in the cell cycle, and it does this by ‘ubiquitinating' proteins — marking them
with ubiquitin. But how do APC/Cs know which proteins to mark?
• "Proteins contain regions known as 'degrons', destruction boxes (D boxes) and KEN
boxes," explains Professor Barford. "The APC/C can then bind to these degrons using
adaptors known as 'coactivators', enabling ubiquitination of the proteins."
• The group's recent work shows the molecular structure of a D box bound to a
coactivator, revealing how these coactivators actually recognise degrons.
• "Being able to show how D boxes are identified on a molecular level has yielded
powerful insights into the processes which regulate the cell cycle," Professor Barford
concludes. "This could ultimately help us to understand the role of APC/C coactivators
in tumour development and to design new drugs which target this mechanism."