Mutations, DNA Repair, and Genomic Instability
Mutation as Change in Information
Types of Mutations
Mutations include substitutions, insertions, deletions, duplications, inversions, and chromosomal rearrangements. Their effects depend on location and context, ranging from silent to lethal or beneficial under specific conditions.
Not All Mutations Are Equal
A single base change can have no effect, reduce function, create a new function, or disrupt regulation entirely.
Repair Pathways
Cells use mismatch repair, base excision repair, nucleotide excision repair, and double-strand break repair to maintain genome integrity. Repair systems detect structural abnormalities, chemical lesions, or strand breaks and restore DNA as accurately as possible.
Common DNA Damage and Responses
| Damage Type | Typical Repair Pathway |
|---|---|
| Base mismatch | Mismatch repair |
| Small chemical lesion | Base excision repair |
| Bulky helix distortion | Nucleotide excision repair |
| Double-strand break | Homologous recombination or end joining |
Which mutation changes a codon but not the encoded amino acid?
Because of redundancy in the genetic code, some substitutions do not change the amino acid.
Correct answer: Silent mutation
Why are double-strand breaks especially dangerous?
Double-strand breaks threaten genome integrity more severely than single-strand lesions.
Correct answer: They can cause chromosome rearrangements, deletions, or cell death if repaired incorrectly.
DNA Damage Response Overview
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1
Step 1: Damage is detected by sensor proteins.
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2
Step 2: Signaling pathways halt the cell cycle if needed.
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3
Step 3: Repair machinery is recruited to the lesion.
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4
Step 4: DNA is restored or the cell undergoes apoptosis if damage is severe.
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Step 5: Genome stability is re-established.
Which pathway best repairs a bulky UV-induced DNA lesion?
Bulky lesions distort the helix and are typically removed by nucleotide excision repair.
Correct answer: Nucleotide excision repair
How can defective DNA repair contribute to cancer?
More mutations raise the chance of activating oncogenes or disabling tumor suppressors.
Correct answer: It increases mutation accumulation and genomic instability.