An improved model for the hTERT promoter quadruplex
Mutations occur at four specific sites in the hTERT promoter in >75% of glioblastomas and melanomas, but the mechanism by which the mutations affect gene expression remains unexplained. We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadrupl...
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| Veröffentlicht in: | PloS one 2014-12, Vol.9 (12), p.e115580-e115580 |
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| creator | Chaires, Jonathan B Trent, John O Gray, Robert D Dean, William L Buscaglia, Robert Thomas, Shelia D Miller, Donald M |
| description | Mutations occur at four specific sites in the hTERT promoter in >75% of glioblastomas and melanomas, but the mechanism by which the mutations affect gene expression remains unexplained. We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadruplex structure consisting of three contiguous, stacked parallel quadruplexes. The reported hTERT mutations map to the central quadruplex within this structure, and lead to an alteration of its hydrodynamic properties and stability. |
| doi_str_mv | 10.1371/journal.pone.0115580 |
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We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadruplex structure consisting of three contiguous, stacked parallel quadruplexes. The reported hTERT mutations map to the central quadruplex within this structure, and lead to an alteration of its hydrodynamic properties and stability.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0115580</identifier><identifier>PMID: 25526084</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Base Sequence ; Biology and Life Sciences ; Cancer ; Cancer genetics ; Circular Dichroism ; Computational Biology - methods ; Computer applications ; Deoxyribonucleic acid ; DNA ; G-Quadruplexes ; Gene expression ; Genomes ; Genomics ; Humans ; Hydrodynamics ; Medicine ; Medicine and Health Sciences ; Melanoma ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Physical Sciences ; Promoter Regions, Genetic ; Telomerase ; Telomerase - chemistry ; Telomerase - genetics ; Telomerase reverse transcriptase</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e115580-e115580</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Chaires et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Chaires et al 2014 Chaires et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-7e4ee303f128805530daaf5c6bb120efe0472c46bc4fc6f4c5977a7ea21f25ef3</citedby><cites>FETCH-LOGICAL-c692t-7e4ee303f128805530daaf5c6bb120efe0472c46bc4fc6f4c5977a7ea21f25ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272262/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272262/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25526084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chaires, Jonathan B</creatorcontrib><creatorcontrib>Trent, John O</creatorcontrib><creatorcontrib>Gray, Robert D</creatorcontrib><creatorcontrib>Dean, William L</creatorcontrib><creatorcontrib>Buscaglia, Robert</creatorcontrib><creatorcontrib>Thomas, Shelia D</creatorcontrib><creatorcontrib>Miller, Donald M</creatorcontrib><title>An improved model for the hTERT promoter quadruplex</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mutations occur at four specific sites in the hTERT promoter in >75% of glioblastomas and melanomas, but the mechanism by which the mutations affect gene expression remains unexplained. We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadruplex structure consisting of three contiguous, stacked parallel quadruplexes. The reported hTERT mutations map to the central quadruplex within this structure, and lead to an alteration of its hydrodynamic properties and stability.</description><subject>Base Sequence</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Circular Dichroism</subject><subject>Computational Biology - methods</subject><subject>Computer applications</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>G-Quadruplexes</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Hydrodynamics</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Melanoma</subject><subject>Models, Molecular</subject><subject>Molecular Dynamics Simulation</subject><subject>Mutation</subject><subject>Physical Sciences</subject><subject>Promoter Regions, Genetic</subject><subject>Telomerase</subject><subject>Telomerase - 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We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadruplex structure consisting of three contiguous, stacked parallel quadruplexes. The reported hTERT mutations map to the central quadruplex within this structure, and lead to an alteration of its hydrodynamic properties and stability.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25526084</pmid><doi>10.1371/journal.pone.0115580</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Base Sequence Biology and Life Sciences Cancer Cancer genetics Circular Dichroism Computational Biology - methods Computer applications Deoxyribonucleic acid DNA G-Quadruplexes Gene expression Genomes Genomics Humans Hydrodynamics Medicine Medicine and Health Sciences Melanoma Models, Molecular Molecular Dynamics Simulation Mutation Physical Sciences Promoter Regions, Genetic Telomerase Telomerase - chemistry Telomerase - genetics Telomerase reverse transcriptase |
| title | An improved model for the hTERT promoter quadruplex |
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