CANCER AND GENES
The fundamental unit that the DNA is organized around is the gene. A gene contains the code for a single protein. Proteins can have many functions ranging from structural, for example, a protein called tubulin which makes the cell’s internal ‘skeleton’, to functional, such as forming the parts of muscles that contract. This flow of information, whereby information in DNA is transcribed into a message (in RNA), and then into a single protein, is one of the central concepts of biology.
Proteins are the key building blocks of cells, responsible for all the key activities. Other components of cells, such as fats and sugars, are manufactured as a result of actions of proteins. Proteins clearly have to have a range of functions, therefore. These include: signalling both within and between cells; structure (a sort of microscopic scaffolding); and, very importantly, proteins called enzymes, which act on other biological molecules to bring about the formation of new molecules. This process can be destructive – for example, the enzymes in digestive secretions (and washing powders!) which break down food; or constructive – the enzymes involved in the manufacture of new molecules for the cell.
The production of a protein from a gene involves the transcription of the gene into a messenger ribose nucleic acid (mRNA) molecule within the nucleus of the cell. The RNA molecule has a structure like DNA but differs in key respects. Firstly, the deoxyribose sugar (the D in DNA) in the backbone is replaced by ribose (the R in RNA). Secondly, the molecule is single-stranded. And thirdly, the thymine (T) base is substituted by uracil (U), though the pairing remains the same.
In order to make RNA, the DNA double helix is temporarily ‘unzipped’ into two single strands. A complementary RNA molecule then assembles and is transported out of the nucleus into the cytoplasm and the DNA then zips itself back up again. This process, another key part of biology, is called transcription.
Once in the cytoplasm, this messenger RNA must be converted into protein, the second key part of the translation of the code embedded in the DNA into functional proteins. The second sort of RNA – called transfer RNA – provides the link between the messenger RNA and the building blocks of protein. Key to this translation process is the triplet code embedded in the DNA. Proteins, like DNA, are made up of chains of simpler molecules. The protein building blocks, called amino acids, can be linked together to form effectively endless chains. The basic amino acid molecule has three key features – termed a carboxy terminus and an amino (hence the name) terminus, plus a variable side branch which gives each amino acid its distinct properties.
Whilst, in theory, an infinite number of types of amino acids are possible, only 20 are found in living organisms. The DNA code is arranged in triplets called codons. There are 64 possible three-letter codes using A, T/U, C, and G. Each triplet has a specific meaning and can either refer to an amino acid or, in effect, form a punctuation mark. For example, within this coding system, AUG means ‘start here’ (termed a ‘start codon’); UAG, UGA, and UAA mean ‘stop here’; while the remainder is linked to specific amino acids – for example, cysteine is UGU or UGC. As there are 64 possible combinations in the triple code but only 20 amino acids, it follows that some amino acids have more than one triplet code. It can easily be seen, therefore, that a mutation which changes a single base can fundamentally alter the resultant protein. For example, a change from UGC (cysteine) to UGA (the stop signal) will shorten the resultant protein, with a possible major change in function.
The core code of the gene is flanked by complex regulatory machinery (see Figure 2) to ensure genes are switched on and off at the correct times. It is this regulation of gene function that is often faulty in the cancer cell.
Regulation of gene expression requires the interaction of a complex series of events. To understand this, a little more detail on gene structure is required.
On both sides of the coding portion of a gene are the control regions. As with a mutation in the coding region described already, it can easily be understood how changes to the regulation of the gene or the processing of the messenger RNA can result in over- or underproduction of a protein or the generation of an abnormal protein with undesirable properties. These control regions are themselves regulated by other genes, called transcription factors, which turn gene expression up or down like a volume control. The transcription factors are the key regulators of the whole process, and it is therefore unsurprising that many of the genes involved in cancer turn out being from this family of proteins.