Question

Mutation and Repair

Discuss the effects of 3 kinds of chemical mutagens and 3 kinds of physical mutagens in Mutation and Repair

Complete the table below

Repair Mechanism	Damage being repaired	Key Enzymes/Proteins for Repair	Mechanism of Repair (key steps only)
Photoreactivation
Base Excision Repair
Mismatch repair
SOS repair

Answer 1

1) The three kinds of chemical mutagens are :

• Reactive oxygen species - Reactive forms of oxygen like superoxide radicals, hydrogen peroxide etc. are produced in the course of normal aerobic reactions. These ROS bring about damage to the DNA like for example oxidation converts guanine to 8-oxy, 7,8-dihydrodeoxyguanine that causes a transversion mutation.
• Deaminating agents - Nitrous acid changes adenine to hypoxanthine by causing induced mutagenesis. This can lead to transition mutation.
• Intercalating agents - Acridine orange, ethidium bromide, dioxin etc are of same size as the nucleotide. They produce mutations by sandwiching themselves between the adjacent DNA bases causing insertions, deletions etc.

The three kinds of physical mutagens are :

• Ionizing Radiation - Gamma or X-ray radiations can penetrate the tissues and damage the DNA structure.
• Ultraviolet radiations - They are responsible in producing pyrimidine dimers and can cause sever damage to the DNA during the process of replication
• Radioactive decay - Radioactive carbon isotope can cause damage to the nitrogen in the nucleotide bases.

2)

Repair mechanism	Damage being repaired	Key enzymes/Proteins	Key steps of repair
Photoreactivation	UV induced pyrimidine dimers	photolyase	The enzyme captures energy from light to break the covalent bonds that link the pyrimidine dimers.
Base excision repair	Modified bases	DNA glycosylases, AP endonucleases, DNA polymerase and DNA ligase	DNA glyccosylase removes the modified base creating an AP site AP endonuclease cuts the phosphodiester bond creating a nick at the site DNA polymerase inserts a new base (dNTPs) in the nicked site and carries on replication DNA ligase seals of the nick in the backbone
Mismatch repair	error in the base incorporation	mutH, mutL, mutS and mutU; exonuclease, DNA polymerase, DNA ligase	The error discovered by mutS mutL binds to mutS and locates the methylation signal mutH endonuclease nicks DNA at a GATC site mutU binds and unwinds the nicked porgeny strand The exonuclease causes digestion of the mismatch base leaving a nick DNA pol III incorporates correct base and DNA ligase seals the nick
SOS repair	UV induced damage causing dsDNA breaks	Rec A protein, LexA protein	Post replicative damage repair involves UV activated SOS box genes SOS activates lexA genes that produces LexA proteins LexA represses other genes but activates RecA RecA fills the post replicative gap in newly synthesized DNA with a strand from undamaged sister duplex