期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 21, 页码 8036-8041出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0601954103
关键词
adenovirus; LINE-1; quiescent cell; hybrid vector
资金
- NCI NIH HHS [R01 CA093709, R01 CA93709] Funding Source: Medline
- NIGMS NIH HHS [R01 GM045398, R01 GM45398, R01 GM60518, R01 GM060518] Funding Source: Medline
Whether long interspersed element-1 (L1 or LINE-1) retrotransposition can occur in quiescent, nondividing, and/or terminally differentiated somatic cells has remained an unanswered fundamental question in human genetics. Here, we used a ubiquitously active phosphoglycerate kinase-1 promoter to drive the expression of a highly active human L1 element from an adenovirus-L1 hybrid vector. This vector system achieved retrotransposition in up to 91% of actively growing immortalized cells, and we demonstrated that L1 retrotransposition can be suppressed by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine. This adenovirus vector enabled efficient delivery of the L1 element into differentiated primary human somatic cells and G(1)/S-arrested cells, resulting in retrotransposition in both cases; however, it was not detected in G(0)-arrested cells. Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells.
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