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Host factors that promote retrotransposon integration are similar in distantly related eukaryotes
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 Schizosaccha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741268/ https://www.ncbi.nlm.nih.gov/pubmed/29232693 http://dx.doi.org/10.1371/journal.pgen.1006775 |
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author | Rai, Sudhir Kumar Sangesland, Maya Lee, Michael Esnault, Caroline Cui, Yujin Chatterjee, Atreyi Ghatak Levin, Henry L. |
author_facet | Rai, Sudhir Kumar Sangesland, Maya Lee, Michael Esnault, Caroline Cui, Yujin Chatterjee, Atreyi Ghatak Levin, Henry L. |
author_sort | Rai, Sudhir Kumar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5741268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57412682018-01-10 Host factors that promote retrotransposon integration are similar in distantly related eukaryotes Rai, Sudhir Kumar Sangesland, Maya Lee, Michael Esnault, Caroline Cui, Yujin Chatterjee, Atreyi Ghatak Levin, Henry L. PLoS Genet Research Article 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. Public Library of Science 2017-12-12 /pmc/articles/PMC5741268/ /pubmed/29232693 http://dx.doi.org/10.1371/journal.pgen.1006775 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Rai, Sudhir Kumar Sangesland, Maya Lee, Michael Esnault, Caroline Cui, Yujin Chatterjee, Atreyi Ghatak Levin, Henry L. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title_full | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title_fullStr | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title_full_unstemmed | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title_short | Host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
title_sort | host factors that promote retrotransposon integration are similar in distantly related eukaryotes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741268/ https://www.ncbi.nlm.nih.gov/pubmed/29232693 http://dx.doi.org/10.1371/journal.pgen.1006775 |
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