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. 1995 May 23;92(11):5199–5203. doi: 10.1073/pnas.92.11.5199

Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications.

X Chen 1, S V Mariappan 1, P Catasti 1, R Ratliff 1, R K Moyzis 1, A Laayoun 1, S S Smith 1, E M Bradbury 1, G Gupta 1
PMCID: PMC41876  PMID: 7761473

Abstract

Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC)n.(GCC)n, are correlated with the ability of the individual G- and C-rich single strands to form hairpin structures. Two-dimensional NMR and gel electrophoresis studies show that both the G- and C-rich single strands form hairpins under physiological conditions. This propensity of hairpin formation is more pronounced for the C-rich strand than for the G-rich strand. This observation suggests that the C-rich strand is more likely to form hairpin or "slippage" structure and show asymmetric strand expansion during replication. NMR data also show that the hairpins formed by the C-rich strands fold in such a way that the cytosine at the CpG step of the stem is C.C paired. The presence of a C.C mismatch at the CpG site generates local flexibility, thereby providing analogs of the transition to the methyltransferase. In other words, the hairpins of the C-rich strand act as better substrates for the human methyltransferase than the Watson-Crick duplex or the G-rich strand. Therefore, hairpin formation could account for the specific methylation of the CpG island in the fragile X repeat that occurs during inactivation of the FMR1 gene during the onset of the disease.

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