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• W2006011870 abstract "Integrated hepadnaviral DNA in livers and tumors of chronic hepatitis B patients has been reported for many years. In this study, we investigated whether hepatitis B virus DNA integration occurs preferentially at sites of cell DNA damage. A single I- Sce I homing endonuclease recognition site was introduced into the DNA of the chicken hepatoma cell line LMH by stable DNA transfection, and double-strand breaks were induced by transient expression of I- Sce I after transfection of an I- Sce I expression vector. Alteration of the target cleavage site by imprecise nonhomologous end joining occurred at a frequency of ≈10 –3 per transfected cell. When replication of an avian hepadnavirus, duck hepatitis B virus, occurred at the time of double-strand break repair, we observed integration of viral DNA at the site of the break with a frequency of ≈10 –4 per transfected cell. Integration depended on the production of viral double-stranded linear DNA and the expression of I -Sce I, and integrated DNA was stable through at least 17 cell divisions. Integration appeared to occur through nonhomologous end joining between the viral linear DNA ends and the I- Sce I-induced break, because small deletions or insertions were observed at the sites of end joining. The results suggest that integration of hepadnaviral DNA in infected livers occurs at sites of DNA damage and may indicate the presence of more widespread genetic changes caused by viral DNA integration itself." @default.
• W2006011870 created "2016-06-24" @default.
• W2006011870 creator A5010547717 @default.
• W2006011870 creator A5025591330 @default.
• W2006011870 date "2004-07-16" @default.
• W2006011870 modified "2023-09-25" @default.
• W2006011870 title "Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration" @default.
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• W2006011870 doi "https://doi.org/10.1073/pnas.0403925101" @default.
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