Most DNA mutations arise from copying errors during DNA replication that the cell's proofreading and repair systems fail to correct.

Is it true that most DNA mutations arise from copying errors during DNA replication that the cell's proofreading and repair systems fail to correct?

Partly. Peer-reviewed sources partially support the claim: yeast and mechanistic work shows replication errors escaping proofreading and mismatch repair become mutations, and one review proposes proofreading inhibition lets replication errors fix as somatic mutations. Other peer-reviewed items attribute substantial mutagenesis to double-strand break repair, transcription-replication conflicts, repair-driven substitutions, and error-prone translesion synthesis, so the evidence covers only part of the picture and points both ways.

Verdict: CONTESTED PARTIAL · 2 sources for, 4 against · Last checked 3 Oct 2026

The private library was unavailable for some searches in this check. Missing library results are not evidence against the claim.

Greene, C. N. & Jinks-Robertson, S. (2001). Spontaneous Frameshift Mutations in <i>Saccharomyces cerevisiae</i>: Accumulation During DNA Replication and Removal by Proofreading and Mismatch Repair Activities. doi.org. https://doi.org/10.1093/genetics/159.1.65

S, D., S, W., N, S., Q, W., S, Z., C, M., E, S., T, C., V, L., L, T., R, B., & JE, H. (2026). Mutations and structural variants arising during double-strand break repair.. doi.org. https://doi.org/10.1073/pnas.2504584123

JJ, B. (2026). Selective Inhibition of DNA Polymerase Proofreading: A Metabolic-Fidelity Mechanism Explains Agent Orange-Associated Myelodysplasia.. doi.org. https://doi.org/10.3390/cancers18172734

E, Z., F, M., YA, B., & K, M. (2026). ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.. doi.org. https://doi.org/10.3390/ijms27167396

For Genomes, Repetition Breeds Diversity. (2011). doi.org. https://doi.org/10.1371/journal.pbio.1001079

A, B., GP, L., RK, P., A, B., B, H., KS, R., S, K., PS, S., A, D., JA, T., & TK, P. (2026). Exploiting DNA damage tolerance for precision oncology.. doi.org. https://doi.org/10.1016/j.trecan.2026.08.003