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Host factors that promote retrotransposon integration are similar in distantly related eukaryotes
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نویسنده
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rai s.k. ,sangesland m. ,lee m. ,esnault c. ,cui y. ,chatterjee a.g. ,levin h.l.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 12
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چکیده
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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. © 2017 public library of science. all rights reserved.
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آدرس
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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,md,united states,division of hematology/oncology,department of medicine,university of florida,gainesville,fl, United States, 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,md,united states,the ragon institute of mgh,mit and harvard,cambridge,ma, United States, jr.,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,md, United States, 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,md, United States, 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,md, United States, 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,md,united states,department of life sciences,presidency university,kolkata,west bengal, India, 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,md, United States
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Authors
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