Mutagenesis mechanisms – sources of frameshifts A frameshift mutation most commonly results from which type of DNA change?
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AFormation of a thymine dimer between adjacent T bases
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BDeamination of cytosine to uracil (C→U)
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CConversion of guanine to xanthine by deamination
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DNone of the above changes directly cause a frameshift; frameshifts typically arise from insertions or deletions not in multiples of 3
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EMethylation of adenine in a promoter
Answer
Correct Answer: None of the above changes directly cause a frameshift; frameshifts typically arise from insertions or deletions not in multiples of 3
Explanation
Introduction / Context:Frameshift mutations alter the reading frame of a coding sequence, changing every downstream codon. Knowing which DNA lesions cause frameshifts is essential for interpreting mutational spectra and their phenotypic outcomes.
Given Data / Assumptions:
- Frameshifts result from insertions or deletions (indels) of 1 or 2 nucleotides (or any number not divisible by 3).
- Base modifications like deamination typically cause base substitutions, not frame changes.
- Pyrimidine dimers distort the helix but do not, by themselves, shift the frame.
Concept / Approach:While thymine dimers and deaminations damage DNA, their direct repair or mispairing outcomes generally produce point mutations (transitions/transversions) rather than frameshifts. Frameshifts are classically associated with replication slippage at short repeats or with intercalating agents (e.g., acridines) that promote single-base indels.
Step-by-Step Solution:Define frameshift: a shift in the triplet reading frame due to indel not divisible by 3.Evaluate listed lesions: thymine dimer (helix distortion), C→U deamination (transition), G→xanthine (mispairs)—none inherently insert/delete nucleotides.Conclude that “none of the above” is correct; frameshifts arise from indels.
Verification / Alternative check:Classic experiments with acridine dyes showed elevated frameshift frequency through single-base insertions/deletions, validating the indel mechanism.
Why Other Options Are Wrong:
- Thymine dimer: blocks polymerases; repaired by excision or photoreactivation; not a frame change per se.
- C→U deamination and G→xanthine: cause base substitutions after replication.
- Methylation in promoters: regulatory modification, not a coding-sequence frameshift.
Common Pitfalls:Equating any DNA damage with frameshift outcomes; only indels alter codon boundaries directly.
Final Answer:None of the above changes directly cause a frameshift; frameshifts typically arise from insertions or deletions not in multiples of 3.