DNA Damage & Repair

Question 1

What are common sources of DNA damage or mutation?

Answer 1

Endogenous: Replication errors, reactive oxygen species, spontaneous base loss

Exogenous: UV radiation, X-rays, chemicals (e.g., tobacco smoke, alkylating agents)

Question 2

How do mutations arise, and what increases their rate?

Answer 2

Mutations arise from errors during DNA replication or repair

Increased by environmental stressors (UV, radiation, mutagens) that damage DNA or disrupt repair mechanisms

Question 3

What is base-excision repair (BER) and what damage does it fix?

Answer 3

Fixes small, non-bulky lesions (e.g., deaminated bases, oxidized bases)

A DNA glycosylase removes the damaged base → AP site is repaired by AP endonuclease, DNA polymerase, and ligase

Question 4

What is nucleotide-excision repair (NER) and what does it fix?

Answer 4

Removes bulky lesions like UV-induced thymine dimers or chemical adducts

Multi-enzyme complex cuts out a short DNA strand around damage → gap filled in by DNA polymerase and sealed by ligase

Question 5

What is mismatch repair (MMR), and what kind of damage does it fix?

Answer 5

Corrects replication errors (e.g., base mismatches or small insertion/deletion loops)

Uses methylation marks to identify the new (incorrect) strand → excises and replaces the mismatch

Question 6

What is non-homologous end joining (NHEJ) and when is it used?

Answer 6

Repairs double-strand breaks by directly ligating the broken ends without using a template

Fast but error-prone → may cause insertions or deletions

Question 7

What is homologous recombination (HR) and when is it used?

Answer 7

Repairs double-strand breaks using a homologous sequence (sister chromatid) as a template

Accurate, but limited to S and G2 phases of the cell cycle

Question 8

What are possible consequences if DNA damage is not repaired?

Answer 8

Mutations → altered proteins

Genome instability → cancer

Cell death (apoptosis)

Senescence (permanent growth arrest)

Hereditary diseases (if in germ cells)

Question 8

Which repair pathway is used for UV-induced thymine dimers?

Answer 8

Nucleotide-excision repair (NER)

Question 9

Which pathway is used for oxidized or deaminated bases?

Answer 9

Base-excision repair (BER)

Question 10

Which repair system corrects errors made during DNA replication?

Answer 10

Mismatch repair (MMR)

Question 11

How does a cell choose between NHEJ and HR for double-strand breaks?

Answer 11

HR if a sister chromatid is available (S/G2 phase)

NHEJ in G1 phase or when rapid repair is needed