Table of contents
Learning Objectives
By the end of this section you should be able to:
- Describe the stages of cell growth.
- Explain cell division.
- Explain cell death.
Introduction
We have learnt that cell is the basic unit of life.
Today, we will be discussing the Cell Cycle.
When we talk about cells, cells grow like we do.
They get bigger, and at some certain stage, they divide into two. This is because a cell must not grow too big.
These processes of growth and division is what is referred to as the Cell cycle and it is a continuous process.
This means that two essential stages are involved in a cell cycle: Cell growth and Cell Division.
When cells divide into two, that means you now have double cells right?
If trillions of cells in the body are dividing into two like that, the body will become congested, it will then lead to severe problems.
This then brings us to Cell death!
Cell death is the complete termination of a cell (either voluntary or induced).
As cells are dividing into two, other cells are dying off, and a cell from the new two replaces the dead cell.
Now you see that cell division and cell death are two important processes that have to go hand in hand.
Infact, about one million cells in animals' bodies die every second. As you are reading this, cells are actively dying in your body. The fact is that these cells die with dignity and there will be problems if they don't.
In summary, cells die, other cells grow, and then divide into two. One then replaces the dead cell.
Why cells must not grow too big
When a cell gets too big, Proteins and other substances are not produced quick enough for a large cell to maintain. Nutrients and wastes will also have a hard time crossing the cell membrane because of the lack of surface area.
The important point is that the surface area to the volume ratio gets smaller as the cell gets larger.
If cells grow beyond a certain limit, not enough material will be able to cross the membrane fast enough to accommodate the increased cellular volume. When this happens, the cell must divide into smaller cells with favorable surface area/volume ratios, or cease to function.
Cell cycle
Most of a Cell's life in a cell cycle is spent in the growth phase known as Interphase.
The shortest phase in a cell cycle is the cell division phase known as Mitosis and Cytokinesis.
Growth phase (Interphase)
When a new cell is formed from a parent cell, it begins to grow in size. This takes about 90% of the cell cycle and three processes are involved,
- G1 phase (“first gap”)
- S phase (“synthesis”)
- G2 phase (“second gap”)
Cell grow during all three phases, but chromosomes are duplicated only during the S phase.
G1 Phase (Gap 1)
In this phase, a cell grows and synthesizes (produces) proteins.
S Phase (Synthesis Phase)
After a cell has produced enough proteins for hours, the cell enters synthesis phase, where its DNA is copied and its chromosome replicates (it multiplies by 2) to make identical copies of itself (sister chromatids) connected by a centromere (joining point). You can read full discussion on DNA replication here
Chromosomes: chromosome is a protein structure that contains the Cell's DNA.
Sister chromatids: Sister chromatids refer to joined copies of a original chromosome. They are identical -
Centromere: The centromere is where the two chromatids are most closely attached.
Many call S phase the cloning phase.
The DNA inside a chromosome is cloned and then another chromosome (protein structure) comes to contain the newly cloned DNA, making it two chromosomes with two DNA (one each) and they're identical.
The chromosomes could have gone their separate ways instantly but there's a bad guy who's still holding them together. Like I said earlier, this bad guy is the centromere.
This cloning happens for the 46 chromosomes that your cells have, making it a total of 92 chromosomes.
The chromosomes remain unclear (not visible) in this S phase.
G2 Phase (Gap 2 Phase)
When the cell is done with replicating its chromosome and DNA, it continues to grow and produce the proteins necessary for cell division.
The Cell also “double checks” the duplicated chromosomes for error, making any needed repair.
Cell Division (Mitosis and Cytokinesis)
Cell Division is the process where the two sister chromatids split and go their separate ways with complete new cells structure.
In other words, during cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei (plural for nucleus).
Cell Division involves two processes:
- Mitosis
- Cytokinesis
Mitosis
Mitosis is the process that involves the separation of sister chromatids in a cell forming two daughter nuclei.
Mitosis occur in all Somatic cells (Cells that are not reproductive cells like sperm or egg cell).
It involves 4 separate phases which I shorten as PMAT
- Prophase
- Metaphase
- Anaphase
- Telophase
PMAT is pronounced as pee–mat. You can try to commit it to memory so you can easily remember anytime.
Prophase
This is the longest phase in Mitosis. What is occuring during this phase is:
All Chromosomes in the cell condenses. This makes the chromosome very clear and visible.
Nuclear membrane disappears.
Centrioles (organelle that produces spindle fibers) separates and move to two opposite ends of the cell.
Spindle fibers form and radiate toward the center of the cell.
Metaphase
This is the Shortest phase in Mitosis. What is occuring during this phase is:
All sister chromatids (double joined chromosome) line up at middle of the cell.
In simple words, the spindle fibers hold each chromosome at the kinetochore on the centromere.
Anaphase
This is the phase where the real splitting starts. What is occuring during this phase is:
The spindle fibers begin to pull the sister chromatids in opposite directions. This process is like attaching ropes to the two sides of a matter and then pulling them in opposite directions to make it split.
Centromeres that join every sister chromatids split. Finally!
Sister chromatids separate becoming individual chromosomes. The sister chromatids are no longer joined by the bad guy (centromere).
Each Separated chromatids (now they are independent) start moving to opposite poles of the cell.
It is important to note that Anaphase will only begin when all kinetochores (on the centromere) have attached to a spindle fiber. If there's any sister chromatids that is not attached to a spindle yet Anaphase will not take place.
Telophase
Telophase is the final phase of mitosis. What is occuring during this phase is:
Chromosomes (each consisting of a single chromatid) uncoil.
A nuclear envelope forms around the chromosomes at each pole of the cell.
Spindle fibers break down and dissolve.
Here, the two new cells look like the opposite sides of an hour glass.
Telophase rounds up Mitosis and Cytokinesis starts immediately.
Cytokinesis
Cytokinesis is the separation of cytoplasm into two individual cells. Each new cell has its own nucleus and organelles.
Cytokinesis involves different process in animal and plant cells:
In animals: cell membrane forms a cleavage furrow that will pinch into two cells.
After Cytokinesis, the two daughter cells finally separate and begin the G1 phase all over again.
Mitosis explained in picture
1. First stage of prophase.
2. Second stage of Prophase.
3. Metaphase.
4. Anaphase.
5. Telophase.
6. Cytokinesis.
One point you should note
Cells may enter a special “resting” phase called G0 or Quiescence phase. Cells in G0 are not actively passing through the cell cycle.
In simple eukaryotes, like yeast, this is often due to lack of nutrients, or a particularly hostile extracellular environment. Under optimal conditions, these primitive cells will pass continuously through the cell cycle and divide.
In advanced, multicellular organisms, lack of nutrients at the cellular level is not a common problem. However, in mature adults, most differentiated cell types rarely divide [which is why you as an adult are growing slowly compared to a young child]. These cells require specific stimuli to prompt them to re-enter the cell cycle and divide again.
In slowly dividing cells, the G1 phase may last months to years. Cells that no longer divide remain arrested in the G1 phase.
Important vocabularies
Centromere: point where sister chromatids are held together.
Chromatid: each of a pair of identical DNA molecules after DNA replication; they are joined at the centromere.
Spindle fibers: fibers that attach to chromosomes and move the chromosomes by pulling homologous chromosomes in opposite directions and pushing the poles apart.
Centrioles: one of a pair of cellular organelles that occur especially in animals, are adjacent to the nucleus, function in the formation of the spindle fiber during cell division.
Microtubules: any of the small tubules in eukaryotic cytoplasm that are composed of the protein tubulin and form an important component of the cytoskeleton, mitotic spindle, cilia, and flagella.
Kinetochores: a specialized structure on the centromere to which the spindle fibers attach during mitosis and meiosis.
Cell Cycle Control
The cell cycle is controlled and regulated by:
- Chemical signals inside and outside the body.
- Physical signals.
- Checkpoint.
Chemical signals
This involves a Cell cycle that is controlled by a chemical control system telling the cell to turn on or off in cell division. It is split in two
Internal Signals- cell senses the presence of enzymes produced within the cell.
External Signals- cells senses presence of chemicals (hormones or growth factors) by specialized cells.
Physical signals
When cells are packed in too closely, division is turned off.
Also, when cells are not in contact with other cells, division will turn on.
Checkpoint
This refers to critical points in the cell cycle where stop and go signals can regulate the cycle.
At these points, the cell can decide if it should go on with division.
Cell division in animal cells is in the “off” position when there is no stimulus present.
Specific stimuli are required to start the process (i.e. growth factors).
Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not respond to signals that normally regulate the cell cycle.
Cancer cells do not need growth factors to grow and divide. They may make their own growth factor
They may convey a growth factor’s signal without the presence of the growth factor.
They may have an abnormal cell cycle control system.
A normal cell is converted to a cancerous cell by a process called Transformation.
Cancer cells that are not eliminated by the immune system form tumours (masses of abnormal cells).
If abnormal cells remain only at the original site, the lump is called a benign tumour.
If abnormal cells move away from the original site and go to attack other cells, the lump is called a Malignant tumour. Malignant tumours invade surrounding tissues and undergo metastasis (exporting cancer cells to other parts of the body, where they may form additional tumours).
Solution for Cancer cells
Radiation Therapy
This therapy uses radiation to kill cancer cells and shrink tumours. Radiation damages the cell’s DNA so that it cannot divide. The radiation is however, usually localized so it won’t kill healthy cells.
Chemotherapy
Uses drugs to kill actively dividing cells and healthy cells.
Travels throughout the entire body.
Cell death
Cell death refers to the complete termination of a cell. Everyday, about 100 billion cells die in our bodies.
Cell death occur in two major forms:
- Apoptosis.
- Necrosis.
Apoptosis
Apoptosis is an active cell death that prevent cells from growing or reproducing. Apoptosis is the kind of “die with dignity” cell death. It is a natural way of neutralizing cell division and it occur intrinsically (from inside the cell) or extrinsically (actions outside the cell). The intrinsic occurrence (or pathway) utilises a protein called Caspases.
Caspases are normally dormant proteins, however, during apoptosis, certain chemicals released by the Mitochondria aim at Caspases, once they interact, Caspases become activated and it disintegrates the cell from within. The apoptotic cell then breaks into small fragments that can be engulfed by other cells.
Necrosis
Necrosis is a passive cell death and it occurs when a cell dies due to shortage of blood or due to a toxin. This is a dangerous kind of cell death and can lead to severe issues if it is left unchecked by the body. A cell that dies by Necrosis can leak out and damage neighbouring cells, and may also trigger inflammation and a massive cellular debris.
Necroptosis
Necroptosis is the combination of Necrosis and apoptosis. Here, a dying cell commits a programmed suicide triggered by some proteins.
Cell death proteins
Caspases
These are proteins that are involved in apoptosis and they digest proteins in a cell to bring about cell death.
Bcl-2 family proteins
These proteins determine whether a cell undergoes Apoptosis or stays alive. They can either block apoptosis and ensure the survival of a cell or they trigger apoptosis.
Death receptors
These proteins attach to the surface of a cell. When they are signaled by cytokines (hormone-like 'cell death trigger' proteins), they cause activities in the cell which can lead to cell death.
RIP kinases
Two proteins known as RIP1 kinase and RIP3 kinase trigger Necroptosis (death of an already dying cell) or Apoptosis.
IAPs
IAPs oppose the activity of Caspases and RIP1 kinase to block Cell death. They are like inhibiting hormones.
SMAC / Diablo
SMAC are stored around the mitochondria and they oppose IAPs. When Apoptosis is triggered, SMAC can block IAPs function (inhibit). Thus, the release of SMAC promote cell death.
What happens to a cell when it dies
Whenever a cell dies, it becomes fragmented and shows signals of "eat me" on its surface.
Phagocytes, which are set of white blood cells come and engulf (they circle around the fragments until it is completely swallowed up inside of them) the dead cells. The dead cells are then transferred to the lysosomes which breaks them down and recycles their components for use.
Summary
📌 Cell cycle is the life of a cell from its formation to its own division.
📌 Cell death is the complete termination of a cell.
📌 The cell cycle consists of the growth phase or interphase and the Cell Division phase.
📌 The growth phase (interphase) takes up about 90% of the cell cycle.
📌 The interphase is split in 3: Gap 1 phase, synthesis phase, Gap 2 phase.
📌 DNA and chromosomes are replicated in the synthesis phase resulting in two sister chromatids for every chromosome, but they are joined together by a centromere.
📌 The Cell division takes about 10% of the cell cycle and it comprises of Mitosis phase and Cytokinesis.
📌 All Cells except sex cells undergo Mitosis.
📌 Mitosis is split into 4, abbreviated as PMAT which are Prophase, Metaphase, Anaphase, Telophase.
📌 Prophase involves setting up the stage and getting ready for division. The chromosomes become clearer and centrioles start moving towards the opposite sides of the cell.
📌 Metaphase is when spindle formation occurs and connect to the centromere of the sister chromatids which have aligned at the centre of the cell.
📌 Anaphase is the splitting stage, sister chromatids finally separate and each moves towards opposite sides of the cell.
📌 Telophase starts when the chromatids reach end of opposite poles, and new cell membrane start forming around the two new cells which are still joined together.
📌 Cytokinesis is the separation of the cytoplasm and the cells are no longer joined together in any way.
📌 Cells which do not need to divide get arrested in the G1 phase or G0 phase.
📌 Cell division is controlled by chemical signals, physical signals and checkpoints inwhich a cell uses stimulus to check if it should continue dividing or stop.
📌 Cancer cells do not respond to the signals that regulate the cell cycle, therefore they continue growing even when they are not supposed to.
📌 Normal cells are changed to cancerous cells by Transformation.
📌 Cancer cells are acted upon by the immune system, and once they overcome the immune system, they become a tumour.
📌 Benign tumour happens when abnormal cells stay where they started from. They do not affect others.
📌 Malignant tumour happens when abnormal cells start to invade other cells and multiplying the number of cancerous cells.
📌 Cancer can be treated by Radiotherapy or Chemotherapy.
📌 Cell death involves two major processes. Apoptosis which is an active cell death or a programmed cell death, and Necrosis which is a passive cell death or a cell death that resulted from attack or shortage of blood.
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Test Questions
1.
Apoptosis is an intrinsic cell death
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