Genomic deletions created upon LINE-1 retrotransposition

Nicolas Gilbert, Sheila Lutz-Prigge, John V. Moran

Research output: Contribution to journalArticlepeer-review

336 Scopus citations

Abstract

LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA. Here, we developed a plasmid-based rescue system and have used it to recover 37 new L1 retrotransposition events from cultured human cells. Sequencing of the insertions revealed the usual L1 structural hallmarks; however, in four instances, retrotransposition generated large target site deletions. Remarkably, three of those resulted in the formation of chimeric L1s, containing the 5′ end of an endogenous L1 fused precisely to our engineered L1. Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence.

Original languageEnglish (US)
Pages (from-to)315-325
Number of pages11
JournalCell
Volume110
Issue number3
DOIs
StatePublished - Aug 9 2002

Bibliographical note

Funding Information:
Correspondence can be addressed to J.V.M. or N.G. We thank members of the University of Michigan DNA Sequencing Core for help with sequencing; Dr. Thomas Glover, Tammy Morrish, and other members of the Moran lab for critically evaluating the manuscript; and Aurélien Doucet and Tara Biagi for excellent technical assistance. This work was supported in part by grants to J.V.M. from the W.M. Keck Foundation, the National Institutes of Health (GM60518), and the March of Dimes. The University of Michigan Cancer Center helped defray some of the DNA sequencing costs.

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