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• W2135180107 startingPage "5675" @default.
• W2135180107 abstract "ABSTRACT Expanded trinucleotide repeats underlie a growing number of human diseases. The human FMR1 (CGG) n array can exhibit genetic instability characterized by progressive expansion over several generations leading to gene silencing and the development of the fragile X syndrome. While expansion is dependent upon the length of uninterrupted (CGG) n , instability occurs in a limited germ line and early developmental window, suggesting that lineage-specific expression of other factors determines the cellular environment permissive for expansion. To identify these factors, we have established normal- and premutation-length human FMR1 (CGG) n arrays in the yeast Saccharomyces cerevisiae and assessed the frequency of length changes greater than 5 triplets in cells deficient in various DNA repair and replication functions. In contrast to previous studies with Escherichia coli , we observed a low frequency of orientation-dependent large expansions in arrays carrying long uninterrupted (CGG) n arrays in a wild-type background. This frequency was unaffected by deletion of several DNA mismatch repair genes or deletion of the EXO1 and DIN7 genes and was not enhanced through meiosis in a wild-type background. Array contraction occurred in an orientation-dependent manner in most mutant backgrounds, but loss of the Sgs1p resulted in a generalized increase in array stability in both orientations. In contrast, FMR1 arrays had a 10-fold-elevated frequency of expansion in a rad27 background, providing evidence for a role in lagging-strand Okazaki fragment processing in (CGG) n triplet repeat expansion." @default.
• W2135180107 created "2016-06-24" @default.
• W2135180107 creator A5036708881 @default.
• W2135180107 creator A5058915559 @default.
• W2135180107 creator A5061678104 @default.
• W2135180107 date "1999-08-01" @default.
• W2135180107 modified "2023-10-15" @default.
• W2135180107 title "Stability of the Human Fragile X (CGG)_n Triplet Repeat Array in <i>Saccharomyces cerevisiae</i> Deficient in Aspects of DNA Metabolism" @default.
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• W2135180107 doi "https://doi.org/10.1128/mcb.19.8.5675" @default.
• W2135180107 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/84419" @default.
• W2135180107 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10409756" @default.
• W2135180107 hasPublicationYear "1999" @default.
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