Abstract:
:Our previous study has shown that recombinant adeno-associated virus (rAAV) vector integrates preferentially in genes, near transcription start sites and CpG islands in mouse liver (H. Nakai, X. Wu, S. Fuess, T. A. Storm, D. Munroe, E. Montini, S. M. Burgess, M. Grompe, and M. A. Kay, J. Virol. 79:3606-3614, 2005). However, the previous method relied on in vivo selection of rAAV integrants and could be employed for the liver but not for other tissues. Here, we describe a novel method for high-throughput rAAV integration site analysis that does not rely on marker gene expression, selection, or cell division, and therefore it can identify rAAV integration sites in nondividing cells without cell manipulations. Using this new method, we identified and characterized a total of 997 rAAV integration sites in mouse liver, skeletal muscle, and heart, transduced with rAAV2 or rAAV8 vector. The results support our previous observations, but notably they have revealed that DNA palindromes with an arm length of greater, similar 20 bp (total length, greater, similar 40 bp) are a significant target for rAAV integration. Up to approximately 30% of total integration events occurred in the vicinity of DNA palindromes with an arm length of greater, similar 20 bp. Considering that DNA palindromes may constitute fragile genomic sites, our results support the notion that rAAV integrates at chromosomal sites susceptible to breakage or preexisting breakage sites. The use of rAAV to label fragile genomic sites may provide an important new tool for probing the intrinsic source of ongoing genomic instability in various tissues in animals, studying DNA palindrome metabolism in vivo, and understanding their possible contributions to carcinogenesis and aging.
journal_name
J Viroljournal_title
Journal of virologyauthors
Inagaki K,Lewis SM,Wu X,Ma C,Munroe DJ,Fuess S,Storm TA,Kay MA,Nakai Hdoi
10.1128/JVI.00963-07subject
Has Abstractpub_date
2007-10-01 00:00:00pages
11290-303issue
20eissn
0022-538Xissn
1098-5514pii
JVI.00963-07journal_volume
81pub_type
杂志文章abstract::The human cytomegalovirus UL4 gene encodes a 48-kDa glycoprotein, expression of which is repressed at the translational level by a short upstream open reading frame (uORF2) within the UL4 transcript leader. Mutation of the uORF2 initiation codon in the viral genome eliminates ribosomal stalling at the uORF2 terminatio...
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pub_type: 杂志文章
doi:10.1128/JVI.75.15.7188-7192.2001
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doi:10.1128/JVI.39.2.390-400.1981
更新日期:1981-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1753-1761.2002
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.53.1.120-127.1985
更新日期:1985-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.3.1697-1705.1994
更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.42.1.317-321.1982
更新日期:1982-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.3.1055-1063.1981
更新日期:1981-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.3.1051-1055.1983
更新日期:1983-06-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.62.8.2531-2536.1988
更新日期:1988-08-01 00:00:00
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2004-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2004-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1987-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1991-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1985-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.2.737-744.1996
更新日期:1996-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1982-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-12-14 00:00:00