MUTATIONS & DNA REPAIR (SET 1)

What are mutations and why are they important?

Mutations are permanent changes in the DNA sequence.

They are the basis for genetic variation and evolution but can also lead to disease if not properly repaired.

What are the main types of DNA mutations?

Point mutations (transitions, transversions)
Insertions/deletions
Inversions
Duplications
Translocations

What are the key causes of mutations?

Spontaneous: replication errors, tautomerism, depurination, deamination
Induced: chemical agents, UV and ionizing radiation, ROS, viral infections

What is tautomerism and how does it cause mutations?

A rare shift in hydrogen atoms on DNA bases causes mispairing during replication, leading to point mutations.

Describe depurination and deamination.

Depurination: loss of a purine (A/G) from DNA
Deamination: conversion of C → U, A → hypoxanthine, leads to incorrect base pairing

Name 3 chemical agents that induce mutations.

Alkylating agents
Intercalating agents
Base analogs

What DNA damage does UV radiation cause?

Formation of thymine dimers, which distort the DNA helix and block replication and transcription.

List the 6 major DNA repair mechanisms.

1. Direct Repair
2. Base Excision Repair (BER)
3. Nucleotide Excision Repair (NER)
4. Mismatch Repair (MMR)
5. Homologous Recombination (HR)
6. Non-Homologous End Joining (NHEJ)
   Translesion Synthesis (TLS)

What is the mechanism of photoreactivation?

Photolyase enzyme uses visible light to reverse UV-induced thymine dimers — Direct repair mechanism.

What is the role of MGMT in DNA repair?

MGMT (O6-methylguanine-DNA methyltransferase) directly removes alkyl groups from guanine to restore DNA.

Silencing via promoter methylation can lead to cancer.

What are the steps in Base Excision Repair (BER)?

1. Recognition by DNA glycosylase
2. AP endonuclease cuts backbone
3. DNA polymerase fills gap
4. DNA ligase seals strand

Nucleotide Excision Repair (NER) is especially effective against what kind of damage?

Bulky DNA lesions and helix-distorting damage (e.g., thymine dimers, chemical adducts)

How does Mismatch Repair (MMR) function?

It identifies and excises mismatched bases after DNA replication. Essential for replication fidelity and preventing microsatellite instability.

Compare Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ).

HR: Uses homologous DNA for error-free repair (S/G2 phase)
NHEJ: Joins broken ends without template, more error-prone (G1 phase)

What is Translesion Synthesis (TLS)?

A repair pathway where specialized polymerases replicate over DNA lesions. It allows bypass of damage but is error-prone.