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Cell cycle

ERICK L NGOSSO
2024

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Learning objectives
 Define cell cycle.
 Explain phases of cell cycle.
 Identify checkpoints presents in cell cycle.
 Identify role of cyclins and cyclins dependent
kinases in cell cycle.

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Definitions of cell cycle

 Cell cycle is the tightly controlled sequence of events


that control processes of DNA replication and mitosis
during cells proliferation.
 Series of events that take place in a cell leading to
duplication of its DNA (DNA replication) and division
of cytoplasm and organelles to produce two daughter
cells (mitosis).
 It is the phase between two consecutive cell
divisions.

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Cell cycle

 The replication of cells is stimulated by growth


factors or by signaling from extracellular matrix
components.
 Each cell cycle phase is dependent on the proper
activation and completion of the previous ones
 It stops at a place at which an essential gene function
is deficient.
 The cell cycle is tightly controlled by activators and
inhibitors.
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Phases of cell cycle

 There are four (4) sequential phases in the cell


cycle:
1. G1 (gap 1) phase.
2. S (synthesis) phase.
3. G2 (gap 2) phase.
4. M (mitotic) phase.

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Phases of cell cycle cont…

G0

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Phases of cell cycle cont…

 Those phases of cell cycle can be grouped into


two (2) main stages:
1. Interphase
 G1 phase.
S phase.
 G2 phase.
2. Mitotic phase
 Mitosis.
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 Cytokinesis.
Phases of cell cycle cont…

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G1 (gap 1) phase
 The first phase within interphase.
 It is from the end of the previous M phase until
the beginning of DNA synthesis.
 G1 (gap 1) phase is also called the presynthetic
phase (first growth phase).
 It is the stage when messenger RNAs for the
proteins and the proteins themselves required
for DNA synthesis (e.g. DNA polymerase) are
synthesised.
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G1 (gap 1) phase cont…
 Thus, the cell increases its supply of proteins,
increases the number of organelles (such as
mitochondria, ribosomes) and grows in size.
 Cells can enter G1 either from G0 (quiescent
cells) or after completing mitosis (continuously
replicating cells).

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S (synthesis) phase
 S phase starts when DNA synthesis commences.
 When this phase is complete, all of the
chromosomes have been replicated.
 Each chromosome has two (sister) chromatids.
 S phase involves replication of nuclear DNA.
 Amount of DNA in the cell has effectively
doubled, though the ploidy of the cell remains
the same.

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G2 (gap 2) phase

 It is also called pre-mitotic phase (second growth


phase).
 G2 phase is a period of protein synthesis and rapid
cell growth to prepare the cell for mitosis.
 During this phase microtubules begin to
reorganize to form a spindle (preprophase).
 It is the short gap phase in which correctness of
DNA synthesised is assessed.
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M (Mitotic) phase

 M phase is the stage in which process of mitosis is


completed and forms two daughter cells.
 Mitotic phase consists of nuclear division
(karyokinesis).
 Mitosis occurs in four (4) sequential stages:
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
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Stages of Mitotic phase
1. Prophase.
 Each chromosome divides into two (2)
chromatids which are held together by
centromere.
 The centriole divides and the two (2) daughter
centrioles move towards opposite poles of the
nucleus
 The nuclear membrane disintegrates.

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Stages of Mitotic phase cont…
2. Metaphase.
 The microtubules become arranged between
the two (2) centrioles forming spindle.
 Chromosomes line up at the equatorial plate of
the spindle.

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Stages of Mitotic phase cont…
3. Anaphase.
 The centromeres divide and each set of
separated chromosomes moves towards the
opposite poles of the spindle.
 Cell membrane also begins to divide.

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Stages of Mitotic phase cont…
4. Telophase.
 There is formation of nuclear membrane around
each set of chromosomes and reconstitution of
the nucleus.
 The cytoplasm of the two daughter cells
completely separates.

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Stages of Mitotic phase cont…

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Stimulation of mitosis

 Stimulation of mitosis can be studied in a number


of ways:
1. Compensatory stimulation of mitosis.
 By removal of part of an organ.
2. Reparative stimulation of mitosis.
 Occurs when a tissue is injured.
3. Target organ stimulation of mitosis.
 Under the influence of specific hormones which have 19
mitogenic effect on cells of the target organ.
Cytokinesis
 Occurs at end of mitosis.
 Division of the cytoplasm to form two (2) new
daughter cells.
 Organelles are divided.
 Daughter cells are genetically identical.

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Stages of Mitotic phase

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G0 (resting) phase

 The cell has left the cycle and stopped dividing.


 Quiescent cells that have not entered the cell cycle
are in the G0 state.
 Non-proliferative (non-dividing) cells enter the
quiescent G0 state from G1.
 These cells may remain quiescent for long periods of
time, possibly indefinitely (e.g. neurons).
 This is very common for cells that are fully differentiated
(permanent cells).
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G0 (resting) phase cont…

 Some cells enter the G0 phase semi-permanently


and are considered post-mitotic, e.g., some liver,
kidney, and stomach cells (stable cells).
 Many cells do not enter G0 and continue to divide
throughout an organism's life, e.g., epithelial
cells (labile cells).
 The daughter cells may continue to remain in the cell
cycle and divide further.
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Phases of cell cycle

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Checkpoints in cell cycle

 Checkpoints typically consist of a network of


regulatory proteins that used by the cell to
monitor and regulate the progress of the cell
cycle.
 Checkpoints prevent cell cycle progression at
specific points, allowing verification of necessary
phase processes and repair of DNA damage.
 Theyensure that damaged or incomplete DNA is not
passed on to daughter cells.
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Checkpoints in cell cycle cont…

 These checkpoints are:


i. During emergence from G0 into G1 (only for quiescent cells).
ii. The transition from G1 to S phase.
iii. The transition from G2 to M phase.
iv. Metaphase (mitotic) checkpoint.

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Checkpoints in cell cycle cont…

 Quiescent cells must first go through the


transition from G0 to G1, which functions as a
gateway to the cell cycle.
 Cells in G1 progress through the cell cycle and
reach a critical stage at the G1 to S transition.
 This is known as a restriction point, a rate limiting step
for replication.
 On passing this restriction point, normal cells become
irreversibly committed to DNA replication.
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Cyclins and Cyclin dependent kinases
(CDKs)
 Progression through the cell cycle in orderly and
directional manner is regulated by proteins called
cyclins.
 Cyclins are associated with enzymes called cyclin
dependent kinases (CDKs).
 CDKs acquire catalytic activity and become active by
binding to and forming complexes with the cyclins.
 Cyclins E, A, B and D appear sequentially during the cell
cycle phases and bind to one or more CDKs. 28
Cell cycle phases, cyclins and CDKs

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Evaluation questions

1. What is an interphase stage?


2. Mention two (2) stages of mitotic phase.
3. Differentiate between karyokinesis from
cytokinesis.
4. Why are checkpoints important in cell cycle?
5. Why do cyclins and cyclin dependent kinases
interact in cell cycle?
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THANK YOU

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