The cell cycle: How the body produces cells

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Cells are produced by the body in a strictly regulated process called the cell cycle. Understanding how the body produces healthy cells is an important foundation for understanding how it produces cancerous cells.1

Cells in the body constantly turnover. That is, old cells die and new ones are produced. Each cell is created to fulfil specific functions in each of the body organs (e.g. specific cells created in the ovaries are different to the cells created in the heart).1 The cell cycle is highly regulated to ensure that the number of cells in the body remains constant. For every cell the body produces, it kills off exactly the same number, except, for example, if the body’s cell requirements change.2

There are many checkpoints in the cell cycle which send signals to cells indicating if they should divide and replicate and if so how,1 and when they should die so that a new cell can take their place.2 These checkpoints are in place to ensure that only healthy, normal cells are produced. If structural errors (e.g. in a cell’s DNA) are found during the cell division, the cell is programmed to rest while it repairs itself. Cancer occurs when one or more of these checkpoints fail, allowing too many cells to grow, or allowing old or abnormally formed cells to continue living.1

Mitosis (cell division)

Mitosis is the division of a cell within any of the body’s tissues. It results in two new cells, which are replicas of the original cell. If the original cell was, for example, situated and functioning in the liver, the two new cells will also be situated in and contain the information needed to fulfil functions in the liver.1

Interphase

Mitosis is a complex process and the cell has to go through a number of stages. They must first progress through an initial gap phase, a synthesis phase and a second (final) gap phase. Collectively these three phases are referred to as the interphase, in which the cell’s integrity is checked and its DNA replicated. Most cells spend much of their lives in the interphase of the cell cycle.1

Gap phase (initial)

The initial gap phase of the cell cycle (also referred to as G1) is the most varied in length, and is one of two gap phases. During the gap phases the cell passes through checkpoints that, when they function correctly, ensure that only healthy, normally formed cells survive.1 The gap phases also provide time for cells to grow and increase the mass of proteins they require to continue progressing through the cell cycle. These processes typically take a lot longer than DNA synthesis and cell division (mitosis).3

Checkpoints in the initial gap phase assess the cell’s internal and external conditions. For example, during the initial gap phase, the environmental conditions are checked to ensure they are favourable for the new cell’s progression through the cell cycle. If the environment is not favourable for cell cycle progression, the cell may be programmed to enter an additional ‘resting’ gap phase known as G0, in which it can wait until favourable conditions arise.1 The majority of cells spend considerable amounts of time in this resting phase.3 When favourable conditions exist, cells in G0 or G1 phases will receive a signal to continue through the cell cycle.1

Synthesis (DNA replication)

Genes contained in cell DNA (deoxyribonucleic acid) provide the information that cells use to reproduce themselves so that they can fulfil their specific roles in the body. In order to create new cells, an existing cell in the body must duplicate its genetic information. This process is called synthesis1 and in mammals usually takes 10-12 hours.3 When it occurs normally, two exact copies of the genetic information contained by the original cell are produced. This prepares the cell for division into two separate cells during the mitosis phase. It is typically considered the first step in the cell cycle.3

Gap phase (final)

Before undergoing mitosis, the cell enters a second and final gap phase, in which it passes further checkpoints which assess the favourability of internal and external conditions. One important check that cells undergo in the final gap phase is performed by a group of proteins which scrutinise the newly synthesised DNA. If the DNA has structural abnormalities or has not been correctly replicated, the cell receives a signal to pause and repair itself before entering the mitosis phase.1

Apoptosis (programmed cell death)

Apoptosis is a genetically determined process of programmed cell death, demolition and removal. It is vital for creating space for new cells and preventing the body from accumulating too many unneeded cells. Around 10 billion cells in the human body die each day, making way for new cells created through mitosis.2 Hence apoptosis is intimately linked to, although not part of, the cell cycle. Many of the proteins and other signals involved in the progression of a cell through the cell cycle are also involved in cell apoptosis.4

Cells that have been programmed to undergo apoptosis begin the process by separating themselves from the surrounding cells and inducing structural change, including fragmentation of their own DNA. This attracts components of the immune system called phagocytes, which digest and dispose of waste materials and foreign particles they find in the body, including old cells which have died.5 Removal of the structural waste by phagocytes prevents an inflammatory reaction to cells undergoing apoptosis, and damage to the surrounding structures.2

Cells may enter the apoptosis phase for a number of reasons, including because they contain damaged DNA. As a cell moves through each stage of the cycle, it may be programmed to undergo apoptosis (i.e. to kill itself) if its structure is not normal. For example, a tumour suppressor gene called p53 can send signals to a cell to repair faulty DNA. If the repair process is unsuccessful, gene p53 can send a further signal that initiates programmed cell death.2

Therefore, apoptosis plays an important role in eliminating abnormal cells which may cause health problems. Dysfunctions that affect the rate of cell apoptosis (either too much or not enough) play an important role in many diseases, including cancer. About half of all cancer patients have dysfunctions affecting the tumour suppressor gene p53.2

 

References

  1. O’Connor C, Adams JU. Unit 5: How do cells know when to divide? Essentials of Cell Biology. Cambridge, MA: NPG Education; 2014. [Book]
  2. Elmore Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. [Full text]
  3. Alberts B, Johnson A, Lewis J, et al. An overview of the cell cycle. Molecular Cell Biology (4th edition). New York: Garland Science; 2002. [Book]
  4. Vermeulen K, Berneman ZN, van Bockstaele DR. Cell cycle and apoptosis. Cell Prolif. 2003;36(3):165-75. [Abstract | Full text]
  5. Taylor RC, Cullen SP, Martin SJ. Apoptosis: Controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008;9(3):231-41. [Abstract | Full text]
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