Session 2: Cell cycle

Session 2: Cell cycle

• Alex Simon (MD)

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Learning tasks

Learning tasks

At the end of this session, students are expected to be able to:

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

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

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

Phases of cell cycle

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

G1 (gap 1) phase.

S (synthesis) phase.

G2 (gap 2) phase.

M (mitotic) phase.

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Phases of cell cycle cont…

Phases of cell cycle cont…

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G0

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Phases of cell cycle cont…

Phases of cell cycle cont…

Those phases of cell cycle can be grouped into two (2) main stages:

Interphase

G1 phase.

S phase.

G2 phase.

Mitotic phase

Mitosis.

Cytokinesis.

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Phases of cell cycle cont…

Phases of cell cycle cont…

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G1 (gap 1) phase

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…

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 (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

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 (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

Prophase

Metaphase

Anaphase

Telophase

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Stages of Mitotic phase

Stages of Mitotic phase

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…

Stages of Mitotic phase cont…

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…

Stages of Mitotic phase cont…

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…

Stages of Mitotic phase cont…

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…

Stages of Mitotic phase cont…

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Stimulation of mitosis

Stimulation of mitosis

Stimulation of mitosis can be studied in a number of ways

Compensatory stimulation of mitosis.

By removal of part of an organ.

Reparative stimulation of mitosis.

Occurs when a tissue is injured.

Target organ stimulation of mitosis.

Under the influence of specific hormones which have mitogenic effect on cells of the target organ.

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Cytokinesis

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

Stages of Mitotic phase

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G0 (resting) phase

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…

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

Phases of cell cycle

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Checkpoints in cell cycle

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.

They ensure that damaged or incomplete DNA is not passed on to daughter cells.

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Checkpoints in cell cycle cont…

Checkpoints in cell cycle cont…

These checkpoints are

During emergence from G0 into G1 (only for quiescent cells).

The transition from G1 to S phase.

The transition from G2 to M phase.

Metaphase (mitotic) checkpoint.

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Checkpoints in cell cycle cont…

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)

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.

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Cell cycle phases, cyclins and CDKs

Cell cycle phases, cyclins and CDKs

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Key points

Key points

Cell cycle involves DNA replication and mitosis.

Phases of cell cycle are G1, S, G2 and M phases.

One cell cycle produce two (2) daughter cells.

Quiescent cells that have not entered the cell cycle are in the G0 state.

Checkpoints ensure the cell cycle proceeds without errors.

G1 to S transition, known as a restriction point, a rate ­limiting step for replication in cell cycle.

Activated CDKs allow cell cycle progression .

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Review questions

Review questions

What is an interphase stage?

Mention two (2) stages of mitotic phase.

Differentiate between karyokinesis from cytokinesis.

Why are checkpoints important in cell cycle?

Why do cyclins and cyclin dependent kinases interact in cell cycle?

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References

References

Kumar V.; Abbas A. K.; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, China. Pg. 181-182.

Mohan H.;(2010): Text book of Pathology (6th Ed.) Jaypee Brothers Medical Publishers, India . Pg. 26-27.

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