دورية أكاديمية
GAA instability in Friedreich's Ataxia shares a common, DNA-directed and intraallelic mechanism with other trinucleotide diseases.
| العنوان: | GAA instability in Friedreich's Ataxia shares a common, DNA-directed and intraallelic mechanism with other trinucleotide diseases. |
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| المؤلفون: | Gacy AM; Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA., Goellner GM, Spiro C, Chen X, Gupta G, Bradbury EM, Dyer RB, Mikesell MJ, Yao JZ, Johnson AJ, Richter A, Melançon SB, McMurray CT |
| المصدر: | Molecular cell [Mol Cell] 1998 Mar; Vol. 1 (4), pp. 583-93. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9802571 Publication Model: Print Cited Medium: Print ISSN: 1097-2765 (Print) Linking ISSN: 10972765 NLM ISO Abbreviation: Mol Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge Ma : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1997- |
| مواضيع طبية MeSH: | Nucleic Acid Conformation* , Trinucleotide Repeats*, Friedreich Ataxia/*genetics, Alleles ; Base Sequence ; DNA/chemistry ; DNA/genetics ; DNA-Directed DNA Polymerase/metabolism ; Family Health ; Friedreich Ataxia/enzymology ; Humans ; Mutation/genetics ; Pedigree ; Recombination, Genetic |
| مستخلص: | We show that GAA instability in Friedreich's Ataxia is a DNA-directed mutation caused by improper DNA structure at the repeat region. Unlike CAG or CGG repeats, which form hairpins, GAA repeats form a YRY triple helix containing non-Watson-Crick pairs. As with hairpins, triplex mediates intergenerational instability in 96% of transmissions. In families with Friedreich's Ataxia, the only recessive trinucleotide disease, GAA instability is not a function of the number of long alleles, ruling out homologous recombination or gene conversion as a major mechanism. The similarity of mutation pattern among triple repeat-related diseases indicates that all trinucleotide instability occurs by a common, intraallelic mechanism that depends on DNA structure. Secondary structure mediates instability by creating strong polymerase pause sites at or within the repeats, facilitating slippage or sister chromatid exchange. |
| معلومات مُعتمدة: | DK 43694-01A2 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 9007-49-2 (DNA) EC 2.7.7.7 (DNA-Directed DNA Polymerase) |
| تواريخ الأحداث: | Date Created: 19980714 Date Completed: 19980728 Latest Revision: 20190914 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/s1097-2765(00)80058-1 |
| PMID: | 9660942 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-2765 |
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| DOI: | 10.1016/s1097-2765(00)80058-1 |