CancerQuest | Impact of Point Mutations

Genetic alterations can be placed into two general categories. The first category is comprised of changes that alter only one or a few nucleotides along a DNA strand. These types of changes are termed point mutations.

When ribosomes read a messenger RNA molecule, every three nucleotides is interpreted as one amino acid. These three letter codes are called codons. To make an analogy to an English sentence: 'The fat cat ate the rat' would contain 6 codons. The changes caused by mutation can lead to things like 'The fat bat ate the rat.' or 'The fa' or 'The fat oca tat her at...' The impact on the protein depends on where the change occurs and the kind of change.

The three-letter codons read by ribosomes may be changed by mutation in one of three ways:

Nonsense mutations

The new codon causes the protein to prematurely terminate, producing a protein that is shortened and often does not function properly or at all.

Missense mutations

The new codon causes an incorrect amino acid to be inserted into the protein. The effects on the function of the protein depend on what is inserted in place of the normal amino acid.

Frameshift mutations

The loss or gain of 1 or 2 nucleotides causes the affected codon and all of the codons that follow to be misread. This leads to a very different and often nonfunctional protein product.

misread mutation

Transcription Errors

Some DNA damage results in a modified nucleotide or small group of nucleotides that can not be 'read' by RNA polymerase. When the RNA polymerase complex reaches these spots they will sometimes bypass the damage by adding in nucleotides in an effort to continue going, even if it means putting in the wrong thing. This process is known as transcriptional mutagenesis and it may play a significant role in the development of cancer.⁽¹⁾