Understanding Cancer: The Importance Of Instructions

Each and every cell in the body contains detailed instructions for its own functioning encoded within its DNA. The DNA is tightly wrapped around special “staple” proteins known as histones and neatly stored in the cell nucleus, which is a large, circular pocket floating in the middle of the cell. Information within the DNA is encoded by the genetic code, which uses 4 simple bases to write the whole handbook on cell biology and life in general. DNA is made up of 4 bases: A (adenine), C (cytosine), G (guanine) and T (thymine). Each group of 3 bases translates to a specific amino-acid: long chains of amino-acids form proteins, which is turn are the building blocks of the cell and take care of all cellular functions, from respiration to movement.

When things go wrong with the DNA code, this has consequences on what kinds of proteins can be formed in the cell. For example, if a bunch of amino-acids is deleted from the genetic blueprint, the protein will be missing a bunch of amino-acids and therefore it is no longer going to be able to carry out its function. Sometimes, bases will be swapped for other bases (for example, and A might be swapped for a G). This means the protein will be produced with different amino-acids and therefore function differently, or not at all. There are two main sources of error in the genetic code: replication and repair.

Cells in our bodies are constantly replicating. Most cells, be their amoebas or members of larger organisms be their animal or vegetable (or fungi!) divide though a process known as mitosis. Before this process can take place, cells make a neat copy of their DNA through a very intricate molecular mechanism known as replication. The DNA is then bundled up into chromosomes and gracefully distributed at the two opposite sides of the cell. The central portion of the cell then contracts, essentially chopping the original “mother” cell into two new “daughter” cells. Thanks to this process, we are able to replace lost cells after an injury, to make new skin to provide us with an ever-changing protective layer and to generate a virtually endless supply of red blood cells and immune cells. Division is essential to life. However, it does come with its dose of danger.

When a cell divides, it is especially vulnerable to random mutation. The process of replication is effectively a molecular exercise in copying down billions of instructions in the form of genetic code – and like any copying exercise it is ridden with opportunities for typos. A “typo” in this context would be a mutated DNA residue, which could have no effect at all but can also result in drastic altering of the genetic blueprint that regulates the life of the cell. It’s easy to understand how this could easily turn into a game of Chinese Whispers, where mutations accumulate in replicating cells until eventually one of them hits a sensitive part of the genetic blueprint and causes cancer.

(From the previous post: Understanding Cancer: The Fountain of Youth)

As well as replication, mutations also arise as a result of botched DNA repair. DNA is constantly subjected to damaging forces, such as UV radiation from the sunshine, X rays and toxins like nicotine and other carcinogenic agents. Fortunately, cells have an in-built repair system that quickly identifies DNA damage and repairs it. However, much like any other DIY repair job, seamless restoration is not guaranteed. In a statistically very small number of cases, the repaired DNA will contain a mistake – originating a potentially cancerous mutation. A second layer of safety ingrained in the functioning of cells is a molecular self-destruct button, which is activated when excessive DNA damage or mutation is detected.

All the molecular machinery involved in replication, damage detection and repair is involved in maintaining the genetic blueprint of the cell in good order. This is known as genomic stability. Whenever a mutation happens in the instructions to make the molecular machinery that is supposed to make sure mutation does not happen, genomic stability is compromised. This means that further mutations can accumulate at a much faster rate, allowing for all the Hallmarks Of Cancer we have examined in this post series to be ticked off. Accumulating mutations will allow cells to start signalling independently and evade programmed cell death, start invading and promote the formation of blood vessels, eventually forming a life-threatening tumor.

The most famous example of such a mechanism are the breast and cervical cancer genes BRCA1 and BRCA2, which were made famous in recent years by Angelina Jolie’s brave stand for women’s health and evidence-driven medicine. The BRCA1 and BRCA2 genes encode for proteins that are in charge of DNA repair – when they are mutated, the DNA in the cell is bare and undefended against damage and random mutation, dramatically increasing the cancer for a tumor to develop.

This post is the last in the series Understanding Cancer. Please check out the first post here and the rest of the posts here. 

 

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