Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus
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{"title"=>"Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus", "type"=>"journal", "authors"=>[{"first_name"=>"Sanggu", "last_name"=>"Kim", "scopus_author_id"=>"37021558600"}, {"first_name"=>"Alice", "last_name"=>"Rusmevichientong", "scopus_author_id"=>"15136968000"}, {"first_name"=>"Beihua", "last_name"=>"Dong", "scopus_author_id"=>"7103180325"}, {"first_name"=>"Roland", "last_name"=>"Remenyi", "scopus_author_id"=>"25636107500"}, {"first_name"=>"Robert H.", "last_name"=>"Silverman", "scopus_author_id"=>"7202370256"}, {"first_name"=>"Samson A.", "last_name"=>"Chow", "scopus_author_id"=>"7201827867"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"359482247", "scopus"=>"2-s2.0-77954539634", "sgr"=>"77954539634", "pmid"=>"20421928", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0010255", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"d0612862-0683-3266-8d26-2e03c4dc2516", "abstract"=>"Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.", "link"=>"http://www.mendeley.com/research/fidelity-target-site-duplication-sequence-preference-during-integration-xenotropic-murine-leukemia-v", "reader_count"=>22, "reader_count_by_academic_status"=>{"Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Other"=>1, "Student > Master"=>1, "Professor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Other"=>1, "Student > Master"=>1, "Professor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Computer Science"=>{"Computer Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/853593"], "description"=>"<p>(A) DNA breaking and joining steps during integration. Viral and target DNA strands are represented by thick black and parallel lines, respectively, and the viral long terminal repeats (LTRs) are depicted as grey boxes. Nucleotides at the top and bottom strands are denoted by uppercase and lowercase letters, respectively. During 3′-end processing, IN removes two nucleotides from the 3′ end of each strand of linear viral DNA so that the viral 3′ ends terminate with a conserved CA dinucleotide. Closed arrowheads denote the positions of strand transfer, a concerted cleavage-ligation reaction during which IN makes a staggered break in the target DNA. Host DNA repair enzymes fill in the resulting single-stranded gaps, denoted by D1 to D4 in the upper strand and d1 to d4 in the lower strand of target DNA, and remove the two unpaired nucleotides at the 5′ ends of the viral DNA (open arrowheads), thereby generating the short direct repeats flanking the provirus. (B) A potential pathway for generating a base transversion in the short direct repeat during XMRV integration. A coordinated integration of the two viral ends occurred at the 4-bp staggered positions as depicted by the closed arrowheads. During repair of the single-stranded gap adjacent to the upstream LTR, an adenine nucleotide was introduced at the D4 position either by misincorporation or aberrant processing of the unpaired AA-dinucleotide at the viral 5′ end. Subsequent repair of the mismatch resulted in the observed transversion (denoted by bold types).</p>", "links"=>[], "tags"=>["retroviral", "dna", "repeats", "flanking"], "article_id"=>524024, "categories"=>["Virology", "Infectious Diseases"], "users"=>["Sanggu Kim", "Alice Rusmevichientong", "Beihua Dong", "Roland Remenyi", "Robert H. Silverman", "Samson A. Chow"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010255.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Integration_of_retroviral_DNA_and_generation_of_short_direct_repeats_flanking_the_provirus_/524024", "title"=>"Integration of retroviral DNA and generation of short direct repeats flanking the provirus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:46:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/853704"], "description"=>"<p>Base compositions of the 4-bp target site duplication (positions D1 to D4; demarcated by the thick vertical lines) and 10 bp upstream (positions −1 to −10) and downstream (positions +1 to +10) of the direct repeat were calculated. The datasets include the 13 integration sites with correct 4-bp direct repeat (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010255#pone-0010255-t001\" target=\"_blank\">Table 1</a>), 472 integration sites from acutely infected DU145 cells (GenBank accession numbers EU981292 to EU981799) and 14 integration sites from human prostate cancer tissues (GenBank accession numbers EU981800 to EU981813) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010255#pone.0010255-Kim1\" target=\"_blank\">[14]</a>. Integration occurs between positions −1 and D1 on the top strand, and between positions D4 and +1 on the bottom strand (blue arrows). Any base in a position that is significantly overrepresented than the random dataset (<i>P</i><0.0001) is highlighted in green, while any base in a position that is significantly underrepresented than the random dataset (<i>P</i><0.0001) is highlighted in red.</p>", "links"=>[], "tags"=>["xmrv"], "article_id"=>524155, "categories"=>["Virology", "Infectious Diseases"], "users"=>["Sanggu Kim", "Alice Rusmevichientong", "Beihua Dong", "Roland Remenyi", "Robert H. Silverman", "Samson A. Chow"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010255.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Base_composition_surrounding_XMRV_integration_sites_/524155", "title"=>"Base composition surrounding XMRV integration sites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:46:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/853777"], "description"=>"<p>*The nucleotide position corresponds to the position of viral DNA insertion at the top strand of the chromosome indicated. Symbols + and – within the parenthesis indicate the orientation of the viral transcription is the same and opposite, respectively, to the polarity of the top strand. GenBank accession numbers for the integration site sequences are GU816075 to GU816104.</p><p>†The left LTR of the provirus contains a 5-bp deletion that includes the conserved CA dinucleotide at the viral end.</p><p>ψThe target DNA contains a T to A transversion immediately adjacent to the left LTR (position 4).</p>", "links"=>[], "tags"=>["xmrv", "sites", "lengths"], "article_id"=>524227, "categories"=>["Virology", "Infectious Diseases"], "users"=>["Sanggu Kim", "Alice Rusmevichientong", "Beihua Dong", "Roland Remenyi", "Robert H. Silverman", "Samson A. Chow"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010255.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positions_of_XMRV_integration_sites_and_lengths_of_the_target_site_sequence_duplication_/524227", "title"=>"Positions of XMRV integration sites and lengths of the target site sequence duplication.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:47:14"}

PMC Usage Stats | Further Information

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