Linked Life Data

7499428

Source:http://linkedlifedata.com/resource/pubmed/id/7499428

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
1996-1-18
pubmed:abstractText
Expansion of a d(CGG)n run within the 5'-untranslated region of the X-linked human gene FMR1 blocks FMR1 transcription, delays its replication, and precipitates the fragile X syndrome. We showed previously that d(CGG)n tracts aggregate into interstrand tetrahelical complexes (Fry, M., and Loeb, L. A. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 4950-4954). Here we show that these sequences also form under physiological conditions in in vitro unimolecular hairpin structures. Folding is demonstrated by temperature-dependent mobility of d(CGG)n oligomers in a nondenaturing polyacrylamide gel, by UV-hyperchromicity of thermally denaturing oligomers, and by UV cross-linking of compact forms of d(CGG)n runs interspersed by thymidine clusters. That the compact d(CGG)n structures are unimolecular is suggested by their zero-order kinetics of formation. Diethyl pyrocarbonate modification reveals a single, 4-5 residue-long central or epicentral unpaired loop in folded d(CGG)n oligomers. The position of this loop remains unchanged by insertion of thymidine clusters into 15- or 33-mer d(CGG) tracts as indicated by KMnO4 probing of unpaired thymidines. The presence of a single loop in folded d(CGG)n oligomers and the accessibility of every guanine to dimethyl sulfate modification suggest that they are hairpin and not tetraplex structures. Modeling indicates that different d(CGG)n hairpins are stabilized by guanine-guanine Hoogsteen hydrogen bonds or by Hoogsteen and Watson-Crick bonds. If formed in vivo, d(CGG)n hairpins could entail slippage and trinucleotide expansion during replication and could obstruct FMR1 gene transcription and replication.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28970-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7499428-Base Sequence, pubmed-meshheading:7499428-Cysteine, pubmed-meshheading:7499428-DNA Replication, pubmed-meshheading:7499428-Diethyl Pyrocarbonate, pubmed-meshheading:7499428-Fragile X Mental Retardation Protein, pubmed-meshheading:7499428-Fragile X Syndrome, pubmed-meshheading:7499428-Guanine, pubmed-meshheading:7499428-Humans, pubmed-meshheading:7499428-Methylation, pubmed-meshheading:7499428-Molecular Probes, pubmed-meshheading:7499428-Molecular Sequence Data, pubmed-meshheading:7499428-Nerve Tissue Proteins, pubmed-meshheading:7499428-Nucleic Acid Conformation, pubmed-meshheading:7499428-Oligodeoxyribonucleotides, pubmed-meshheading:7499428-RNA-Binding Proteins, pubmed-meshheading:7499428-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:7499428-Transcription, Genetic
pubmed:year
1995
pubmed:articleTitle
The fragile X syndrome single strand d(CGG)n nucleotide repeats readily fold back to form unimolecular hairpin structures.
pubmed:affiliation
Unit of Biochemistry, Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't