Hairpins are formed by the single DNA strands of the fragile X triplet repeats: Structure and biological implications
- Los Alamos National Lab., Los Alamos, NM (United States)
- Univ. of California, Davis, CA (United States)
Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC){sub n}{center_dot}(GCC){sub 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 {open_quotes}slippage{close_quotes} 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{center_dot}C paired. The presence of a C{center_dot}C mismatch at the CpG site generates local flexibility, thereby providing analogs of the transition to the methyltransferease. 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. 18 refs., 7 figs, 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 75386
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 11 Vol. 92; ISSN PNASA6; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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