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- W2174508949 endingPage "gkv1008" @default.
- W2174508949 startingPage "gkv1008" @default.
- W2174508949 abstract "Unusual DNA/RNA structures of the C9orf72 repeat may participate in repeat expansions or pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded repeats are CpG methylated with unknown consequences. Typically, quadruplex structures form by G-rich but not complementary C-rich strands. Using CD, UV and electrophoresis, we characterized the structures formed by (GGGGCC)8 and (GGCCCC)8 strands with and without 5-methylcytosine (5mCpG) or 5-hydroxymethylcytosine (5hmCpG) methylation. All strands formed heterogenous mixtures of structures, with features of quadruplexes (at pH 7.5, in K+, Na+ or Li+), but no feature typical of i-motifs. C-rich strands formed quadruplexes, likely stabilized by G•C•G•C-tetrads and C•C•C•C-tetrads. Unlike G•G•G•G-tetrads, some G•C•G•C-tetrad conformations do not require the N7-Guanine position, hence C9orf72 quadruplexes still formed when N7-deazaGuanine replace all Guanines. 5mCpG and 5hmCpG increased and decreased the thermal stability of these structures. hnRNPK, through band-shift analysis, bound C-rich but not G-rich strands, with a binding preference of unmethylated > 5hmCpG > 5mCpG, where methylated DNA-protein complexes were retained in the wells, distinct from unmethylated complexes. Our findings suggest that for C-rich sequences interspersed with G-residues, one must consider quadruplex formation and that methylation of quadruplexes may affect epigenetic processes." @default.
- W2174508949 created "2016-06-24" @default.
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- W2174508949 date "2015-10-01" @default.
- W2174508949 modified "2023-10-12" @default.
- W2174508949 title "Quadruplex formation by both G-rich and C-rich DNA strands of the<i>C9orf72</i>(GGGGCC)8•(GGCCCC)8 repeat: effect of CpG methylation" @default.
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- W2174508949 doi "https://doi.org/10.1093/nar/gkv1008" @default.
- W2174508949 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4787773" @default.
- W2174508949 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26432832" @default.
- W2174508949 hasPublicationYear "2015" @default.
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