3 - Mechanisms of Mutation (Spontaneous & Induced)

Question 1

What are nucleotides known to be modified by

Answer 1

• Oxidative damage
• Hydrolytic attack
• Uncontrollled methylation

Question 2

Chemical stability of DNA

Answer 2

• DNA is subject to hydrolysis, oxidation, and non enzymatic methylation in vivo
• These changes interfere with regular base pairing and/or the physical structure of DNA

Question 3

Tautomers

Answer 3

• Structural isomers that readily interconvert with the relocation of a proton
• Tautomeric shifts allow for irregular base pairing

Question 4

Mutagens

Answer 4

Agents that cause an increase in the rate of mutation (x rays, UV, chemicals, viruses)

Question 5

Mechanisms of mutagens

Answer 5

• Alkylation
• Depurination
• Base analogs
• Deamination

Question 6

Deaminating agents

Answer 6

• Deamination can be spontaneous or induced
• Methyl-Cytosine becomes T
• Nitrous acid is a potent driver of oxidative deamination

Question 7

Alkylating agents

Answer 7

• Chemicals that donate alkyl groups to other molecules
• Cause transitions, transversions, frameshifts, and chromosome aberrations

Question 8

Depurination

Answer 8

• Hydrolysis reactions remove purine rings by cleaving the N-glycosidic bond that holds them to the sugar
• If not repaired before replicated, any base may be added or position may be deleted

Question 9

Intercalating agent

Answer 9

• Thin, plate-like hydrophobic molecules insert themselves between adjacent base pairs
• +’vely charged molecules
• Mutagenic intercalating agents cause
  insertions during DNA replication.
• Loss of intercalating agent can result in deletion.

Question 10

Examples of intercalating agents

Answer 10

• Proflavin
• Ethidium bromide

Question 11

Base analogues

Answer 11

• Similar structures to regular DNA bases
• When incorporated into DNA, they increase frequency of mis-pairing

Question 12

UV radiation

Answer 12

• Causes purines and pyrimidines to form abnormal dimer bonds with adjacent bases and bulges in DNA strands (thymine dimers most common)
• Block DNA replication and activates repair mechanisms

Question 13

Ionising radiation

Answer 13

• X-rays, gamma rays, alpha and beta particles
• Can produce double strand breaks, abasic sites and single strand breaks