Linked Life Data

20800555

Source:http://linkedlifedata.com/resource/pubmed/id/20800555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Telomeres consisting of tandem guanine-rich repeats can form secondary DNA structures called G-quadruplexes that represent potential targets for DNA repair enzymes. While G-quadruplexes interfere with DNA synthesis in vitro, the impact of G-quadruplex formation on telomeric repeat replication in human cells is not clear. We investigated the mutagenicity of telomeric repeats as a function of G-quadruplex folding opportunity and thermal stability using a shuttle vector mutagenesis assay. Since single-stranded DNA during lagging strand replication increases the opportunity for G-quadruplex folding, we tested vectors with G-rich sequences on the lagging versus the leading strand. Contrary to our prediction, vectors containing human [TTAGGG]?? repeats with a G-rich lagging strand were significantly less mutagenic than vectors with a G-rich leading strand, after replication in normal human cells. We show by UV melting experiments that G-quadruplexes from ciliates [TTGGGG]? and [TTTTGGGG]? are thermally more stable compared to human [TTAGGG]?. Consistent with this, replication of vectors with ciliate [TTGGGG]?? repeats yielded a 3-fold higher mutant rate compared to the human [TTAGGG]?? vectors. Furthermore, we observed significantly more mutagenic events in the ciliate repeats compared to the human repeats. Our data demonstrate that increased G-quadruplex opportunity (repeat orientation) in human telomeric repeats decreased mutagenicity, while increased thermal stability of telomeric G-quadruplexes was associated with increased mutagenicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1568-7856
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1119-29
pubmed:dateRevised
2011-11-10
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Telomeric repeat mutagenicity in human somatic cells is modulated by repeat orientation and G-quadruplex stability.
pubmed:affiliation
Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, PA 15219, United States.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural