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Analysis of 5′ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5′-end attachment requiring microhomology-mediated end-joining

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Zingler, Nora, Willhoeft, Ute, Brose, Hans-Peter, Schoder, Volker, Jahns, Thomas, Hanschmann, Kay-Martin O., Morrish, Tammy A., Löwer, Johannes, Schumann, Gerald G.·2005·Genome Research

DOI 10.1101/gr.3421505PMC PMC1142468

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Abstract

Insertion of the human non-LTR retrotransposon LINE-1 (L1) into chromosomal DNA is thought to be initiated by a mechanism called target-primed reverse transcription (TPRT). This mechanism readily accounts for the attachment of the 3′-end of an L1 copy to the genomic target, but the subsequent integration steps leading to the attachment of the 5′-end to the chromosomal DNA are still cause for speculation. By applying bioinformatics to analyze the 5′ junctions of recent L1 insertions in the human genome, we provide evidence that L1 uses at least two distinct mechanisms to link the 5′-end of the nascent L1 copy to its genomic target. While 5′-truncated L1 elements show a statistically significant preference for short patches of overlapping nucleotides between their target site and the point of truncation, full-length insertions display no distinct bias for such microhomologies at their 5′-ends. In a second genome-wide approach, we analyzed Alu elements to examine whether these nonautonomous retrotransposons, which are thought to be mobilized through L1 proteins, show similar characteristics. We found that Alu elements appear to be predominantly integrated via a pathway not involving overlapping nucleotides. The results indicate that a cellular nonhomologous DNA end-joining pathway may resolve intermediates from incomplete L1 retrotransposition events and thus lead to 5′ truncations.

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Authors: Zingler, N., Willhoeft, U., Brose, H.-P., Schoder, V., Jahns, T., Hanschmann, K.-M. O., Morrish, T. A., Löwer, J., & Schumann, G. G.
Affiliations: Paul Ehrlich Institut (DE)
Universität Hamburg (DE)
University Medical Center Hamburg-Eppendorf (DE)
University of Michigan (US)
ORCID: Willhoeft, Ute
Schoder, Volker
Morrish, Tammy A.
Schumann, Gerald G.
Venue: Genome Research
Publisher: Cold Spring Harbor Laboratory
Published: 2005-06
Volume: 15
Issue: 6
Pages: 780-789
ISSN: 1088-9051 (ISSN-L)
DOI: 10.1101/gr.3421505
PMC: PMC1142468
OpenAlex: W2041586254
Cited by: 111
References: 59
Citations by year: 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 1 · 2019: 4 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 8 · 2013: 3 · 2012: 2
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: Genome Research (publishedVersion, other-oa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
National Institutes of Health
National Institute of General Medical Sciences (GM60518, R01GM060518)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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 retrotransposons, Alu elements, microhomology-mediated end joining, non-homologous end joining, target-primed reverse transcription, retrotransposition
MeSH terms: Chromosomes, Human, DNA Replication, Humans, Models, Genetic, Recombination, Genetic, Sequence Homology, Nucleic Acid, Genome, Human, Mutagenesis, Insertional, Long Interspersed Nucleotide Elements, Alu Elements

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Analysis of 5′ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5′-end attachment requiring microhomology-mediated end-joining

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