title: Holliday Junctions Are Associated with Transposable Element Sequences in the Human Genome.
abstract: Holliday junctions (HJs) constitute important intermediate structures for many cell functions such as DNA recombination and DNA repair. They derive from a 10-nt degenerate sequence, with a 3-nt core motif. In this study, we explored the human genome whether the HJ degenerate sequence associates with transposable elements (TEs) and mainly with those of the active and inactive ALU, LINE, SVA and HERV families. We identified six different forms of the HJ sequence motif, and we located the genomic coordinates of sequences containing both HJs and TEs. From 2982 total HJs, a significant number of 1319 TE-associated HJs were found, with a median distribution of 1 per 2.4 Mb. The HJs with higher GC content were observed more frequently at the genome. A high percentage of HJs were associated with all main TE families, with specificity for particular active or inactive elements: DNA elements and the retroelements ALUs, LINEs and HERVs up to 41.94%, 72.72%, 42.94% and 84.5%, respectively. Phylogenetic analysis revealed that HJs occur in both active and inactive TEs. Furthermore, the TE-associated HJs were almost exclusively found within a distance less than 1 Mb from human genes, while only 23 were not associated with any genes. This is the first report associating human HJs, with mobile elements. Our data pinpoint that particular HJ forms show preference for specific active retrotransposon families of ALUs and LINEs, suggesting that retrotransposon-incorporated HJs may relocate or replicate in the genome through retrotransposition, contributing to recombination, genome plasticity and DNA repair.
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece.
authors.forename: Paris
authors.initials: P
authors.lastname: Ladias
authors.affiliation: Laboratory of General Biology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Markopoulos
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece.
authors.forename: Leandros
authors.initials: L
authors.lastname: Lazaros
authors.affiliation: Department of Neurology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Markoula
authors.affiliation: Laboratory of General Biology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Tzavaras
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine, University of Ioannina, 54 110 Ioannina, Greece. Electronic address: igeorgio@uoi.gr.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiou
mesh_terms: D001483:Base Sequence; D004260:DNA Repair; D004251:DNA Transposable Elements; D045566:DNA, Cruciform / Q000737:chemistry / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D010802:Phylogeny; D011995:Recombination, Genetic; D018626:Retroelements
chemical_list: D004251:DNA Transposable Elements; D045566:DNA, Cruciform; D018626:Retroelements
keywords: ALU; DNA repair; HERV; Holliday junctions (HJ); LINE; SVA; inverted repeats (IR); mobile elements; recombination; retroelements