Mutagenesis pathways

“Mutagenesis pathways” is not a single molecule, receptor, enzyme, or discrete drug target, but a broad, conceptual term encompassing the various cellular processes and molecular mechanisms that generate heritable DNA sequence changes (mutations).[2][3] Mutagenesis itself is the process by which an organism’s genetic information is altered, either spontaneously (endogenous DNA damage, replication errors) or in response to environmental mutagens such as chemicals, radiation, or certain biological agents.[3][5][7] At the cellular level, mutation formation is tightly linked to DNA damage, DNA replication, and DNA repair or damage-bypass mechanisms: cells experience continuous DNA damage from endogenous sources (e.g., reactive oxygen species) and exogenous mutagens, and then engage multiple DNA damage response and repair pathways—base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and non-homologous end joining (NHEJ)—plus lesion-bypass translesion synthesis (TLS) polymerases (e.g., REV1, POLζ, POLη, POLκ, POLι).[2][3][6][8][12] Errors during replication across damaged templates (error‑prone TLS) and inaccurate repair (particularly NHEJ and some stress‑induced or “adaptive” mutagenesis programs) convert DNA lesions into fixed mutations.[2][3][12] Collectively, these mechanistic routes by which DNA lesions are misreplicated or misrepaired are what is typically meant by “mutagenesis pathways.” They are central to fundamental biology (evolution and genetic diversity) but also to disease, because deregulation or failure of DNA repair and damage response pathways causes genome instability, contributes to carcinogenesis, stress‑induced mutagenesis in microbes, emergence of antibiotic resistance, and has been implicated in certain neurodegenerative disorders involving repeat instability.[2][3][8][12]

Other names

Mutagenesis mechanismsDNA mutagenesis pathwaysMechanisms of mutagenesisPathways of DNA damage–induced mutagenesis