Journal Article

L1 Retrotransposition in Nondividing and Primary Human Somatic Cells

Kubo, Shuji, Perez, José Luis Garcia, Soifer, Harris S., Kasahara, Noriyuki, Seleme, Maria del Carmen, Moran, John V., Kazazian, Haig H.

2006

Overview

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 G₁/S-arrested cells, resulting in retrotransposition in both cases; however, it was not detected in Go-arrested cells. Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells.

• Publisher: National Academy of Sciences
• Subject: Adenoviridae - genetics / Adenovirus / Adenoviruses / Base Sequence / Biological Sciences / Cell Cycle / Cell growth / Cell Line, Tumor / Cell lines / Cells / Enzyme Inhibitors - pharmacology / Gene expression / Genetic Vectors / Genetics / Hepatocytes / Humans / Infections / Long Interspersed Nucleotide Elements / Models, Genetic / Molecular Sequence Data / Phosphoglycerate Kinase - metabolism / Plasmids / Retroelements / Somatic cells / Transfection / Viruses