Genomic Deletions Created upon LINE-1 Retrotransposition
Open accessAbstract
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.
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L1 retrotransposon activity has been linked to DNA damage, mutagenesis, and deregulation of host gene transcription.
“Long interspersed element 1 (L1) retrotransposon activity, in particular, has been linked to DNA damage5, mutagenesis6,7, and deregulation of host gene transcription8.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [6]
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- Authors
- Gilbert, N., Lutz-Prigge, S., & Moran, J. V.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Moran, John V.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 110
- Issue
- 3
- Pages
- 315-325
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2002190096
- Cited by
- 474
- References
- 1
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 11 · 2023: 17 · 2022: 21 · 2021: 12 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 25 · 2016: 20 · 2015: 28 · 2014: 19 · 2013: 18 · 2012: 13
- FWCI
- 39.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM60518, R01GM060518)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- LINE-1 retrotransposition, insertional mutagenesis, human genome
- MeSH terms
- Base Sequence, Cloning, Molecular, Eukaryotic Cells, Genetic Engineering, HeLa Cells, Humans, Molecular Sequence Data, Mutation, Polymorphism, Genetic, Recombinant Fusion Proteins, Genome, Human, Mutagenesis, Site-Directed, Gene Deletion, DNA, Complementary, Retroelements, Long Interspersed Nucleotide Elements
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