DNA damage, repair and mutation

Question 1

What is a mutation?

Answer 1

A change in the DNA sequence of an organism

Question 2

What are mutations caused by?

Answer 2

Substitutions, insertions or deletions

Question 3

What is the effect of substitutions?

Answer 3

Substitution affects 1 codon, hence affects 1 amino acid.

Question 4

What is the effect of insertions or deletions?

Answer 4

These have a bigger effect than substitutions as they change the whole reading frame and have the potential to change every amino acid downstream from the insertion/deletion.

Question 5

What is the process of damage and repair?

Answer 5

Healthy dividing cell –> damage to cell –> damage control (stop cell division, damage assessment, DNA repair) –> either successful repair (return to cell cycle) OR extensive damage (cell death) –> failed repair (damage accumulates - cancer)

Question 6

What are the types of mutations?

Answer 6

• Single base changes (point mutations)
• Nucleotide insertions
• Nucleotide deletions
• Duplication of sequences
• Larger-scale chromosomal rearrangements

Question 7

What are the causes of mutations?

Answer 7

1) Endogenous damage
* Errors in nucleotide incorporation during DNA replication
* Damage induced by oxidative metabolism and hydrolytic damage

2) Exogenous damage
* Chemically-induced
* Radiation-induced

Question 8

How do replication errors occur?

Answer 8

Misincorporation, which is when the wrong base is added to the daughter strand. If this is repaired, it is no problem, but if this new daughter strand is replicated, the DNA polymerase will not recognise the mistake and the damaged section will be replicated.

Question 9

Which 3 mechanisms ensure replication accuracy?

Answer 9

1) The accuracy of the DNA polymerase
2) The proofreading mechanism contained within the DNA polymerase that will remove incorrect nucleotides and replace them with correct ones
3) Mismatch repair

Question 10

What are mutagens?

Answer 10

Agents that cause mutation.

Question 11

What are examples of chemical and radiative mutagens?

Answer 11

Chemical
* cigarette smoke
* asbestos
* free radicals & oxidising agents

Radiation
* Ultraviolet rays from the sun
* Natural radioactivity
* Nuclear waste, bombs
* Medical X-rays

Question 12

What are thymine dimers?

Answer 12

DNA damage caused by UV rays of sunlight. Results in covalent linking of adjacent thymine bases - no longer can properly base pair with other bases.

Question 13

What are some types of changes and their effects?

Answer 13

1) No effect: results in a different codon that prescribes the same amino acid (AA)
2) Missense: results in a change in AA identity
3) Nonsense: results in a new stop signal
4) Insertion/deletion of nucleotides:
* Frameshift: gives a completely new downstream AA sequence. May introduce a new stop signal.
5) Insertion/deletion of a multiple of 3 bp
* Results in gain/loss of AAs

Question 14

What happens to a protein with a changed amino acid sequence?

Answer 14

1) It depends on the amino acid
* Some amino acids are very similar while some have very different side chain properties.

2) It depends on the protein
* Loss of function may result e.g a less active/inactive enzyme
* Gain of function may result e.g the protein gains a new activity