23 Review of DNA Transcription, Translation and Types of DNA Mutations

DNA Transcription and Translation

It is often said that DNA contains the blueprint for the cell as it used to construct enzymes and proteins required for enabling and facilitating cellular reactions, cellular signalling, as well as building cellular components.  There are 23 pairs of chromosomes containing over 20,000 genes altogether, which are used to code for proteins and peptides.  In brief, DNA transcription and translation involves the process of converting genetic information first from DNA into mRNA and then into functional proteins.   Transcription is the process in which a gene is copied into a complimentary strand of messenger RNA (mRNA).  Translation involves the mRNA sequence of nucleotides being used to string specific amino acids together to form proteins.  In this section we will examine how mutations in DNA can affect the proteins being produced.   

The Effects of DNA Mutation on Protein Production

As mentioned in the previous section, mutations in genes can occur due to various factors such as viruses, asbestos, radiation, cigarette smoke, or spontaneous errors during DNA duplication.  There are several types of mutations that can occur on a strand of DNA and some can have significant effects, while other may not have any effect at all.

In examining the effects of DNA mutations, we need to remember that genes are spread along chromosomes at times separated by sequences of non-coding regions.  These non-coding regions don’t code for peptides or proteins, but can play other roles.  For example, non-coding regions contain promotor regions that influence the rate of transcription of downstream genes.  Some non-coding DNA is used to make non-coding RNA such as transfer RNA (tRNA) and ribosomal RNA (rRNA) molecules.   There are other non-coding regions that don’t appear to have any function at all and is referred to as “junk DNA”, though that is currently under investigation as non-coding DNA makes up over 98% of our genome.  Over millennia, “junk DNA” it may be that some DNA used to have purposes, that are no longer required.  It may too, that junk DNA has been perpetually inserted into the genome over time and been passed from one generation to the other.  Some of this junk DNA likely came from pre-historic viruses and bacteria.

Point Mutations and Frameshift Mutations and Cancer

There are 3 types of mutations include insertion, substitution, and deletion mutations.  Point mutations are the most common type of mutation and involve a substitution of a single nucleotide in DNA.  A substitution mutation replaces one nucleotide with another (e.g. CAG to CAT), potentially altering one amino acid in the protein though not always.  There are 3 possible outcomes.  A point mutation can create a silent, missense or nonsense mutation as shown in the table below.

The table above gives examples of point mutations that are classified as silent, missense and nonsense depending on the effect on the protein produced.  A silent mutation occurs when the nucleotide substitution does not change the amino acid that is coded for and is therefore sometimes called a synonymous mutation.  A missense mutation results in a new amino acid being coded for and its effects depend on whether the new amino acid changes the function of the protein or enzyme.  There be no effect on the protein/enzyme’s ability to function.  However, there may be a loss of function or even a change of function that actively impedes cellular abilities or structure.  Nonsense mutations result in a protein or enzyme that is either not functional or actively dysfunctional.  In this case, unless the cell produces other similar proteins or enzymes that are able to compensate for this loss, the cell itself could become less functional, function inappropriately, or even die.  Due to the difference created in the final peptide sequence, both missense and nonsense mutations are considered nonsynonymous mutations.

Frameshift mutations occur when a nucleotide is either inserted or deleted within a gene’s coding region.  As a result, there is a shift in the reading frame affecting the mRNA sequence that is transcribed and then translated.  As a result of a frameshift, all of the DNA’s reading frames downstream of the mutation will be affected, potentially resulting in every subsequent codon as being different and coding for a different amino acid.

In the above examples of point mutations and frameshift mutations, it is evident the substitution, insertion or deletion of an amino acid within the coding region can lead to loss of a functional protein or enzyme.  In the case of cancer, over 290 gene mutations have been identified which affect the function of key enzymes – most often those involved in regulating the rates of cell cycling, differentiation and apoptosis.

Chromosomal Alterations

Chromosomal alterations often result in death of the cell or organism (depending on the stage of development in which it occurs rather than cancer. Chromosomal alterations involve sections of DNA either being deleted, duplicated, inverted, translocated (from one region of the chromosome to another), or inserted (added).

Think about questions

Are most cancers caused by sporadic (spontaneous) or acquired mutations?

Are most cancer caused by inherited mutations?