DNA repair mediated by endonuclease-independent LINE-1 retrotransposition
Top Cited Papers
- 13 May 2002
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 31 (2) , 159-165
- https://doi.org/10.1038/ng898
Abstract
Long interspersed elements (LINE-1s) are abundant retrotransposons in mammalian genomes that probably retrotranspose by target site-primed reverse transcription (TPRT)1,2. During TPRT, the LINE-1 endonuclease cleaves genomic DNA3, freeing a 3′ hydroxyl that serves as a primer for reverse transcription of LINE-1 RNA by LINE-1 reverse transcriptase. The nascent LINE-1 cDNA joins to genomic DNA, generating LINE-1 structural hallmarks such as frequent 5′ truncations, a 3′ poly(A)+ tail and variable-length target site duplications (TSDs)2. Here we describe a pathway for LINE-1 retrotransposition in Chinese hamster ovary (CHO) cells that acts independently of endonuclease but is dependent upon reverse transcriptase. We show that endonuclease-independent LINE-1 retrotransposition occurs at near-wildtype levels in two mutant cell lines that are deficient in nonhomologous end-joining (NHEJ). Analysis of the pre- and post-integration sites revealed that endonuclease-independent retrotransposition results in unusual structures because the LINE-1s integrate at atypical target sequences, are truncated predominantly at their 3′ ends and lack TSDs. Moreover, two of nine endonuclease-independent retrotranspositions contained cDNA fragments at their 3′ ends that are probably derived from the reverse transcription of endogenous mRNA. Thus, our results suggest that LINE-1s can integrate into DNA lesions, resulting in retrotransposon-mediated DNA repair in mammalian cells.Keywords
This publication has 27 references indexed in Scilit:
- Mammalian LINE‐1 Retrotransposons and Related ElementsPublished by American Society for Microbiology ,2007
- Human L1 Retrotransposition: cisPreference versus trans ComplementationMolecular and Cellular Biology, 2001
- A Transient Assay Reveals That Cultured Human Cells Can Accommodate Multiple LINE-1 Retrotransposition EventsAnalytical Biochemistry, 2000
- Many human L1 elements are capable of retrotranspositionNature Genetics, 1997
- High Frequency Retrotransposition in Cultured Mammalian CellsCell, 1996
- Human L1 Retrotransposon Encodes a Conserved Endonuclease Required for RetrotranspositionCell, 1996
- Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaksNature, 1996
- The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombinationCell, 1995
- Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: A mechanism for non-LTR retrotranspositionCell, 1993
- Dispersal process associated with the L1 family of interspersed repetitive DNA sequencesJournal of Molecular Biology, 1984