[PMID]: | 29232693 |
[Au] Autor: | Rai SK; Sangesland M; Lee M; Esnault C; Cui Y; Chatterjee AG; Levin HL |
[Ad] Endereço: | Section on Eukaryotic Transposable Elements, Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, United States of America. |
[Ti] Título: | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes. |
[So] Source: | PLoS Genet;13(12):e1006775, 2017 12. |
[Is] ISSN: | 1553-7404 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements. |
[Mh] Termos MeSH primário: |
Fatores Hospedeiros de Integração/genética Recombinação Genética Retroelementos/genética Sequências Repetidas Terminais/genética Ubiquitina-Proteína Ligases/genética
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[Mh] Termos MeSH secundário: |
Reparo do DNA/genética Eucariotos/genética Regulação Fúngica da Expressão Gênica Integrases/genética Regiões Promotoras Genéticas DNA Polimerase Dirigida por RNA/genética Retroviridae/genética Saccharomyces cerevisiae/genética Proteínas de Saccharomyces cerevisiae/genética Schizosaccharomyces/genética
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (Integration Host Factors); 0 (Retroelements); 0 (Saccharomyces cerevisiae Proteins); 0 (Spp382 protein, S cerevisiae); EC 2.3.2.27 (Rhp18 protein, S pombe); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.7.- (Integrases); EC 2.7.7.49 (RNA-Directed DNA Polymerase); EC 2.7.7.49 (reverse transcriptase Ty3, S cerevisiae) |
[Em] Mês de entrada: | 1801 |
[Cu] Atualização por classe: | 180111 |
[Lr] Data última revisão:
| 180111 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171213 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pgen.1006775 |
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