General Biology I
Chapter 14 Mutation, DNA Repair, and Cancer or Life in a Fallen World
Mutations are permanent, heritable changes to the DNA.
Point Mutations – changes to nucleotide sequence of individual genes.
Chromosomal Mutations – changes to the gene order of chromosomes.
Point/Gene Mutations:
Substitution Mutations replace one Nucleotide with another.
When one Nucleotide is substituted for another, one codon in the resulting RNA will be altered.
Typically, this will alter one amino acid in the resulting Protein.
The change of one amino acid could produce little to no effect, or a lethal one.
It is also possible the codon could be changed to a stop codon and end the Protein prematurely.
This would most likely destroy the Protein’s function.
It is also possible, because of the redundancy of the Genetic Code that the new
codon would code for the same amino acid.
The Protein would not be changed and function normally (Silent Mutation).
a. Additions - add one or more nucleotides to a gene.
b. Deletions - delete one or more nucleotides from a gene.
Both produce Frameshift Mutations
Frameshift Mutations - shifts the triplet reading frame of the codons.
Mutations outside Coding Regions:
Mutations outside the Region Coding for the Nucleotides of the RNA can also have effects.
These mutations often affect the regulation of genes.
Only mutations in the Germ line cells are passed on to individuals of the next generation.
Mutations in Somatic (or body) cells are not.
Somatic Mutations like cancers, can have serious health effects for the individual, but
only the individual, not their children.
Mutations may be of natural cause (spontaneous) or from outside factors (induced).
Mutagens are chemicals or physical factors that alter the structure of DNA.
Nucleic Acids are chemicals and can enter into reactions which convert them to
something other than the normal four bases of DNA.
Nitrous Oxide (found in smoked meats) can remove the amino group from Cytosine
or Adenine, replacing it with a carbonyl group to produce Uracil and Hypoxanthine.
Cytosine normally pairs with Guanine, but when converted to Uracil, pairs with Adenine.
C-G pair is converted to a U-A (T-A) pair, a substitution mutation.
Adenine normally pairs with Thymine, but when converted to Hypoxanine, pairs with Cytosine.
A-T pair is converted to a H-C (G-C) pair a substitution mutation.
Base Analogues - similar enough to the "real" DNA bases to be incorporated into DNA,
but they don't have the same faithfulness in pairing.
Produce Substitution Mutations.
Ionizing Radiation (X-rays) physically cut DNA which may not be repaired correctly.
Bases could be removed, strands could be cut.
UV light has high enough energy to promote covalent linkages between
adjacent Pyrimidine bases (T-T dimers).
DNA Polymerase does not recognize the dimer as a normal base and will randomly insert one.
Substitution mutations are promoted.
DNA Repair:
Nucleotide Excision Repair is one of the more widespread and better understood mechanisms.
UvrABA Complex scans DNA looking for errors, such as Thymine dimers.
When found, UvrB releases UvrA and recruits UvrC.
UvrC cuts the sugar-phosphate backbone on either side of the mutation.
Then, UvrD (a helicase) is recruited to remove the damaged section from one cut to the other.
Finally, DNA Polymerase replaces the damaged removed section, using the intact,
undamaged strand as a template.
Finis
