L1 retrotransposition in nondividing and primary human somatic cells

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

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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 G0-arrested cells. Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells.

Original languageEnglish (US)
Pages (from-to)8036-8041
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number21
DOIs
StatePublished - May 23 2006
Externally publishedYes

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Long Interspersed Nucleotide Elements
Adenoviridae
Phosphoglycerate Kinase
Gastrin-Secreting Cells
Reverse Transcriptase Inhibitors
Zidovudine
Medical Genetics

Keywords

  • Adenovirus
  • Hybrid vector
  • LINE-1
  • Quiescent cell

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

L1 retrotransposition in nondividing and primary human somatic cells. / Kubo, Shuji; Del Carmen Seleme, Maria; Soifer, Harris S.; Perez, José Luis Garcia; Moran, John V.; Kazazian, Haig H.; Kasahara, Noriyuki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 21, 23.05.2006, p. 8036-8041.

Research output: Contribution to journalArticle

Kubo, Shuji ; Del Carmen Seleme, Maria ; Soifer, Harris S. ; Perez, José Luis Garcia ; Moran, John V. ; Kazazian, Haig H. ; Kasahara, Noriyuki. / L1 retrotransposition in nondividing and primary human somatic cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 21. pp. 8036-8041.
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