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Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts
To aid in the characterization of the relationship of structure and function for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT), this investigation utilized DNAs containing benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-modified primers and templates as a probe of the archi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778021/ https://www.ncbi.nlm.nih.gov/pubmed/24069141 http://dx.doi.org/10.1371/journal.pone.0072131 |
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author | Chary, Parvathi Beard, William A. Wilson, Samuel H. Lloyd, R. Stephen |
author_facet | Chary, Parvathi Beard, William A. Wilson, Samuel H. Lloyd, R. Stephen |
author_sort | Chary, Parvathi |
collection | PubMed |
description | To aid in the characterization of the relationship of structure and function for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT), this investigation utilized DNAs containing benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-modified primers and templates as a probe of the architecture of this complex. BPDE lesions that differed in their stereochemistry around the C(10) position were covalently linked to N (6)-adenine and positioned in either the primer or template strand of a duplex template-primer. HIV-1 RT exhibited a stereoisomer-specific and strand-specific difference in replication when the BPDE-lesion was placed in the template versus the primer strand. When the C(10) R-BPDE adduct was positioned in the primer strand in duplex DNA, 5 nucleotides from the 3΄ end of the primer terminus, HIV-1 RT could not fully replicate the template, producing truncated products; this block to further synthesis did not affect rates of dissociation or DNA binding affinity. Additionally, when the adducts were in the same relative position, but located in the template strand, similar truncated products were observed with both the C(10) R and C(10) S BPDE adducts. These data suggest that the presence of covalently-linked intercalative DNA adducts distant from the active site can lead to termination of DNA synthesis catalyzed by HIV-1 RT. |
format | Online Article Text |
id | pubmed-3778021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37780212013-09-25 Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts Chary, Parvathi Beard, William A. Wilson, Samuel H. Lloyd, R. Stephen PLoS One Research Article To aid in the characterization of the relationship of structure and function for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT), this investigation utilized DNAs containing benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-modified primers and templates as a probe of the architecture of this complex. BPDE lesions that differed in their stereochemistry around the C(10) position were covalently linked to N (6)-adenine and positioned in either the primer or template strand of a duplex template-primer. HIV-1 RT exhibited a stereoisomer-specific and strand-specific difference in replication when the BPDE-lesion was placed in the template versus the primer strand. When the C(10) R-BPDE adduct was positioned in the primer strand in duplex DNA, 5 nucleotides from the 3΄ end of the primer terminus, HIV-1 RT could not fully replicate the template, producing truncated products; this block to further synthesis did not affect rates of dissociation or DNA binding affinity. Additionally, when the adducts were in the same relative position, but located in the template strand, similar truncated products were observed with both the C(10) R and C(10) S BPDE adducts. These data suggest that the presence of covalently-linked intercalative DNA adducts distant from the active site can lead to termination of DNA synthesis catalyzed by HIV-1 RT. Public Library of Science 2013-09-19 /pmc/articles/PMC3778021/ /pubmed/24069141 http://dx.doi.org/10.1371/journal.pone.0072131 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Chary, Parvathi Beard, William A. Wilson, Samuel H. Lloyd, R. Stephen Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title | Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title_full | Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title_fullStr | Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title_full_unstemmed | Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title_short | Inhibition of HIV-1 Reverse Transcriptase-Catalyzed Synthesis by Intercalated DNA Benzo[a]Pyrene 7,8-Dihydrodiol-9,10-Epoxide Adducts |
title_sort | inhibition of hiv-1 reverse transcriptase-catalyzed synthesis by intercalated dna benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide adducts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778021/ https://www.ncbi.nlm.nih.gov/pubmed/24069141 http://dx.doi.org/10.1371/journal.pone.0072131 |
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