Mutagenesis mechanisms – sources of frameshifts A frameshift mutation most commonly results from which type of DNA change?

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.