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• W2023167598 endingPage "13453" @default.
• W2023167598 startingPage "13448" @default.
• W2023167598 abstract "Naturally occurring DNA sequences can form noncanonical structures such as H-DNA, which are abundant and regulate the expression of several disease-linked genes. Here, we show that H-DNA-forming sequences are intrinsically mutagenic in mammalian cells. This finding suggests that DNA is a causative factor in mutagenesis and not just the end product. By using the endogenous H-DNA-forming sequence found in the human c-myc promoter, mutation frequencies in a reporter gene were increased approximately 20-fold over background in COS-7 cells. H-DNA-induced double-strand breaks (DSBs) were detected near the H-DNA locus. The structures of the mutants revealed microhomologies at the breakpoints, consistent with a nonhomologous end-joining repair of the DSBs. These results implicate H-DNA-induced DSBs in c-myc gene translocations in diseases such as Burkitt's lymphoma and t(12;15) BALB/c plasmacytomas, where most breakpoints are found near the H-DNA-forming site. Thus, our findings suggest that H-DNA is a source of genetic instability resulting from DSBs and demonstrate that naturally occurring DNA sequences are mutagenic in mammals, perhaps contributing to genetic evolution and disease." @default.
• W2023167598 created "2016-06-24" @default.
• W2023167598 creator A5004046021 @default.
• W2023167598 creator A5053366417 @default.
• W2023167598 date "2004-09-01" @default.
• W2023167598 modified "2023-10-04" @default.
• W2023167598 title "Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells" @default.
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• W2023167598 doi "https://doi.org/10.1073/pnas.0405116101" @default.
• W2023167598 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/518777" @default.
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