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Twin Priming: A Proposed Mechanism for the Creation of Inversions in L1 Retrotransposition
Open accessAbstract
L1 retrotransposons are pervasive in the human genome. Approximately 25% of recent L1 insertions in the genome are inverted and truncated at the 5′ end of the element, but the mechanism of L1 inversion has been a complete mystery. We analyzed recent L1 inversions from the genomic database and discovered several findings that suggested a mechanism for the creation of L1 inversions, which we call twin priming. Twin priming is a consequence of target primed reverse transcription (TPRT), a coupled reverse transcription/integration reaction that L1 elements are thought to use during their retrotransposition. In TPRT, the L1 endonuclease cleaves DNA at its target site to produce a double-strand break with two single-strand overhangs. During twin priming, one of the overhangs anneals to the poly(A) tail of the L1 RNA, and the other overhang anneals internally on the RNA. The overhangs then serve as primers for reverse transcription. The data further indicate that a process identical to microhomology-driven single-strand annealing resolves L1 inversion intermediates.
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Citations
Cites
Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition
Feng, Q., Moran, J. V., Kazazian, H. H., & Boeke, J. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81997-2 · Cited by 1,139
Self-citation
Cited by
Mobile Elements: Drivers of Genome Evolution
Kazazian, H. H. (2004) · Science · doi:10.1126/science.1089670 · Cited by 1,922
Self-citationRoles for retrotransposon insertions in human disease
Hancks, D. C., & Kazazian, H. H. (2016) · Mobile DNA · doi:10.1186/s13100-016-0065-9 · Cited by 670
Self-citationLINE-1 elements in structural variation and disease
Beck, C. R., Garcia-Perez, J. L., Badge, R. M., & Moran, J. V. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082509-141802 · Cited by 615
Transposable elements in cancer
Burns, K. H. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.35 · Cited by 572
Human L1 element target‐primed reverse transcription in vitro
Cost, G. J., Feng, Q., Jacquier, A., & Boeke, J. D. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf592 · Cited by 519
Metadata
- Authors
- Ostertag, E. M., & Kazazian, H. H.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2001-12-01
- Volume
- 11
- Issue
- 12
- Pages
- 2059-2065
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- OpenAlex
- W2151097873
- Cited by
- 254
- References
- 1
- Type
- posted content
- Language
- en
- Open access
- bronze
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- Ostertag, E. M., & Kazazian, H. H. (2001). Twin Priming: A Proposed Mechanism for the Creation of Inversions in L1 Retrotransposition. Genome Research. https://doi.org/10.1101/gr.205701
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