Analysis of 5′ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5′-end attachment requiring microhomology-mediated end-joining
| Autor: | Hans-Peter Brose, Volker Schoder, Tammy A. Morrish, Ute Willhoeft, Thomas Jahns, Nora Zingler, Kay-Martin Hanschmann, Johannes Löwer, Gerald Schumann |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
DNA Replication
Alu element Retrotransposon Computational biology Biology Genome chemistry.chemical_compound Alu Elements Sequence Homology Nucleic Acid Genetics Chromosomes Human Humans Letters Genetics (clinical) Recombination Genetic Models Genetic Genome Human DNA replication Reverse transcriptase Mutagenesis Insertional Microhomology-mediated end joining Long Interspersed Nucleotide Elements chemistry Human genome DNA |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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