6.1.1 - Mutagen operations

Question 1

Mutation overview

Answer 1

• Change in the sequence of nucleotides in DNA
• Can be naturally occurring, e.g. spontaneous mistakes during DNA replication, or induced by environmental factors, e.g. UV light and exposure to cigarette smoke

Question 2

Mutagens

Answer 2

• Agents that cause mutations by altering DNA
• E.g. UV light, chemicals, biological agents, or naturally occurring mutagens
• The process of inducing a mutation is called mutagenesis

Question 3

Chemical mutagens

Answer 3

• Chemicals that cause mutations if cells are exposed to them at high frequencies over a sustained period of time
• Come from free radicals, which are molecules with unpaired electrons. ⭐Free radicals can take electrons from DNA to become stable, but losing an electron destabilises the DNA molecule. This can cause single-strand or double-strand breaks in the DNA, disrupting genetic information and interfering with correct DNA replication and repair.
• Free radicals can be present in ingested chemicals and environmental irritants
• Ingested chemical mutagens: alcohol, tobacco smoke tar, food additives and preservatives etc.
• Environmental irritants and poisons: benzene and other organic solvents, cleaning products, asbestos, pesticides etc.

⭐ Due to the instability of the valence shell, free radicals are highly reactive and will capture electrons from other sources to fulfil the octet rule.

Question 4

Mispairing

Answer 4

• Mispairing is the insertion of incorrect nucleotides opposite other nucleotides during DNA replication
• Can occur as chemical mutagens are usually similar in structure to the normal purine and pyrimidine bases of DNA. As a result, they can mistakenly become incorporated into DNA during replication
• Mispairing often results in the production of a non-functional protein

Question 5

Naturally occuring mutagens

Answer 5

• Mutagenic agents that are present at normal levels within the natural environment
• Prolonged exposure to naturally occurring mutagens increases the risk of mutagenesis
• Comprises two groups: biological and non-biological mutagens

• Biological mutagens: e.g. viruses, bacteria, fungi
• Non-biological mutagens: e.g. cadmium and mercury

Question 6

Biological mutagens

Answer 6

End products of metabolism

• Carcinogenic nitrosamines are formed when food containing nitrites are eaten together with amines. When these foods are cooked at high temperatures, the nitrites and amines combine to form nitrosamines

Microbes

• Are naturally occurring biological mutagens. Includes viruses like hepatities B, HIV, and Rubella, as well as bacteria like Helicobacter pylori, which causes stomach ulcers.
• They can insert their own base sequences into DNA, changing the functioning of genes and triggering cancers
• Some bacteria or their products cause inflammation, which allows free radicals to be produced and potentially damage DNA.

Question 7

Physical mutagens

Answer 7

• Comprises ionising radiation and heat

UV

• UVA is non-ionising but still mutagenic given prolonged exposure to it
• UVB and UVC have shorter wavelengths and have high energy for ionisation
• The ionisation of two consecutive Ts or Cs will cause them to bond to one another rather than their opposite nucleotides. This distorts the shape of the DNA molecule to form dimers

X-rays and Gamma rays

• Have extremely high energy, allowing them to break the sugar-phosphate backbone of a DNA strand
• This break can occur as a single-strand break or a double-strand break
• Radiation can also cause mutations indirectly by causing other molecules to lose an electron (free radicals). These molecules are reactive intermediates that then interact with DNA to induce mutations

Question 8

DNA self repair enzymes

Answer 8

Damage to DNA is quite common, but the body’s defense mechanism repairs mutations constantly.

The DNA repair system involves 3 enzymes:
1. Exonuclease: removes damaged sections of DNA
2. DNA polymerase: adds the missing bases
3. Ligase: repairs the break in the sugar-phosphate backbone

These enzymes operate during DNA replication to proofread copying errors, and continuously repair spontaneous damage to DNA

Question 9

DNA repair mechanisms

Answer 9

Base excision repair

• A nuclease enzyme removes a damaged or incorrectly paired base from its sugar linakge and replaces it

Mismatch repair

• DNA polymerase checks the accuracy of replication once DNA replication has concluded

Nucleotide excision repair

• Exonuclease cuts out the damaged DNA segment, polymerase fills in the missing nucleotide, and ligase seals the sugar-phosphate backbone
• Nucleotide excision repair is used in repairing bulky DNA damage, such as UV-induced thymine dimers