4 - Mechanism of Mutation (Errors of DNA Replication & Repair)

Question 1

What types of abnormalities need repair

Answer 1

• Base mismatches
• Damage to the structure of DNA itself (e.g. breaks in chromosome or pyrimidine dimers)

Question 2

Direct DNA repair

Answer 2

• Single strand breaks (DNA ligase can rejoin backbone)
• Enzymatic repair (highly specific removal of chemical groups)

Question 3

Base Excision Repair (BER)

Answer 3

• Base specific DNA glycosylase remove altered base
• AP endonuclease removes sugar back bone
• DNA polymerase replaces missing nucleotide
• DNA ligase seals ssDNA break

Question 4

Nucleotide Excision Repair (NER)

Answer 4

• Detects and repairs distortions in the DNA helix
• Excision nuclease removes nucleotides in and around the distortion
• DNA polymerase replaces the missing nucleotides
• DNA ligase seals the ssDNA break

Question 5

Mismatch Repair

Answer 5

• Corrects post-replicative base-pair mismatches
  and insertion/deletion loops
• Complex scans DNA for single strand break
• Exonuclease removes up to 1000bp of strand
• DNA polymerase replaces the missing nucleotides
• DNA ligase seals the ssDNA break

Question 6

Slippage

Answer 6

• Repeating regions effected, (e.g. microsatellites)
• DNA polymerase “slips off” and misaligns with a nearby repeat
• Creates distortion in helix which should be detected and repair by mismatch system
• Replication before repair will produced a new allele

Question 7

Homologous Recombination (HR)

Answer 7

• Due to radiation, ROS, stalled replication forks
• Can repair double strand breaks
• Mutations in HR associated genes can be pathogenic

Question 8

Non Homologous End joining

Answer 8

• Double strand break repair
• Multiple rounds of resection and addition possible
• Can repair double strand breaks without loss/change

Question 9

Transition mutations

Answer 9

Purine-purine or pyrimidine-pyrimidine substitution

Question 10

Transversion mutation

Answer 10

purine-pyrimidine substitution or vice versa

Question 11

Missense mutation

Answer 11

Causes one amino acid to replace another

Question 12

Nonsense mutation

Answer 12

Creates premature stop codon at site of mutation

Question 13

Gain of function mutations

Answer 13

Expressed at incorrect time or in inappropriate cell types

Question 14

Splice mutation

Answer 14

A mutation that affects the pattern of RNA splicing, thereby changing the content of the mRNA