Nucleic Acids Research, Vol 24, Issue 4 784-792, Copyright © 1996 by Oxford University Press
SV Mariappan, P Catasti, X Chen, R Ratliff, RK Moyzis, EM Bradbury and G Gupta
Three-dimensional structures of the fragile X triplet repeats (GCC)n and
(GGC)n are derived by using one- dimensional/two-dimensional NMR. Under a
wide range of solution conditions (10-150 mM NaCl,pH6-7)(GCC)5- 7 strands
form exclusively slipped hairpins with a 3' overhanging C. The slipped
hairpins of (GCC)n strands show the following structural characteristics:
(i) maximization of Watson-Crick G.C pairs; (ii) formation of C.C mispairs
at the CpG steps in the stem; (iii) C2'-endo, anti conformations for all
the nucleotides. The ability of (GCC)n strands to form hairpin structures
more readily than complementary (GGC)n strands suggests preferential
slippage during replication and subsequent expansion of the (GCC)n strands.
In addition, the C.C. mispairs at the CpG site of (GCC)n hairpins account
for their exceptional substrate efficiencies for human methyltransferase.
Gel electrophoresis data show that (GGC)n strands form both hairpin and
mismatched duplex structures in 10-150 mM NaCl (ph 6-7) for n < 10, but
for n > or + 11 hairpin structures are exclusively present. However,
(GGC)n strands remain predominantly in the duplex state for n=4-11 under
NMR solution conditions, which require DNA concentrations 100- to 1000-fold
higher than in gel electrophoresis. NMR analyses of [(GGC)n]2 duplexes for
n=4-6 show the presence of Watson-Crick G.C and mismatched G anti G syn
pairs. The mismatches adjacent to the CpG step introduce local structural
flexibility in these duplexes. Similar structural properties are also
expected in the stem of the hairpins formed by (GGC)n strands.
ARTICLES
Solution structures of the individual single strands of the fragile X DNA triplets (GCC)n.(GGC)n
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
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