Nomadic genetic elements contribute to oncogenic translocations: Implications in carcinogenesis  Sridaran Dhivya, Kumpati Premkumar  Critical Reviews in Oncology / Hematology  Volume 98, Pages 81-93 (February 2016) DOI: 10.1016/j.critrevonc.2015.10.012 Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 TE Distribution. Pictorial representation of TE distribution (in percentages) in the genes and within their neighborhood. Percentages based on the data available in (Miki et al., 1992)MER—Medium Reiterated frequency sequence, ERVE—Endogenous Retrovirus. Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Diagrammatic representation of prominent transposons in the Human Genome. (a) LINE (Long Interspersed Element)—L1 has 2 open reading frames (ORFs) that encode RNA-binding proteins, endonuclease and reverse transcriptase flanked by untranslated regions(UTR). (b) SINE (Short Interspersed Element)—Alu has a left monomer with internal RNA polymerase III promoter (A&B box) and a right monomer separated by an A-rich connector. (c) LTR Retrotransposon such as HERV (Human endogenous retrovirus) has the Long Terminal Repeats flanking the GAG, POL and ENV genes encoding for capsid protein, protease, polymerase and envelop protein. (d) Mariner has the DNA-binding domain and DDE catalytic domain that encode transposase. It is flanked by inverted repeats (IR). DDE—conserved DDE sequence of Mariner transposase. NLS—Nuclear Localisation Signal. Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 Effects of TE insertion. From left to right-insertion of TE within the exons cause a change protein synthesis, within the regulatory region of genes cause up/down-regulation of the gene, within the intronic regions causes very minimal effect on the functionality of the gene. Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 4 TE induced Double Strand Break Repair mechanism. Diagrammatic representation of the classic Double Strand Break Repair mechanism emphasizing Homologous Recombination.TE insertion induced strand break is repaired initiating synthesis of nascent DNA by the formation of Holliday junctions undergoing crossover and non-crossover (Kines and Belancio, 2012; Resnick, 1976; Sorek et al., 2002). Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 5 Non-homologous allelic recombination. Non-homologous allelic recombination (NHAR) results in TE insertion by three mechanisms-gain of gene segments occurs on sister chromatid exchange, rearrangement within the same chromosome causes inversion of gene segments, chromosomal rearrangements within the homologous chromosomes results in exchange of chromosomal regions (Resnick, 1976; Sen et al., 2006; Ferguson and Holloman, 1996; Lee et al., 2005). Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 6 Break-Induced Repair. TE induces Single Strand Annealing where a few nucleotides are chewed back at the 5′ end and homologous chromosomes anneal and ligate leaving behind a deleted region (Neves et al., 1999; Sawyer and Malik, 2006). Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions

Fig. 7 Telomere specific Transposon Insertion. Repair after TE insertion in the telomeric region occurs forming “d-loop” followed by non-homologous end joining and strands annealing. Critical Reviews in Oncology / Hematology 2016 98, 81-93DOI: (10.1016/j.critrevonc.2015.10.012) Copyright © 2015 Elsevier Ireland Ltd Terms and Conditions