Nucleic Acids Research, Vol 24, Issue 11 1992-1998, Copyright © 1996 by Oxford University Press
J Petruska, N Arnheim and MF Goodman
Expansions of trinucleotide repeats in DNA, a novel source of mutations
associated with human disease, may arise by DNA replication slippage
initiated by hairpin folding of primer or template strands containing such
repeats. To evaluate the stability of single-strand folding by repeating
triplets of DNA bases, thermal melting profiles of (CAG)10, (CTG)10,
(GAC)10 and (GTC)10 strands are determined at low and physiological salt
concentrations, and measurements of melting temperature and enthalpy change
are made in each case. Comparisons are made to strands with three times as
many repeats, (CAG)30 and (CTG)30. Evidence is presented for stable
intrastrand folding by the CAG/CTG class of triplet repeats. Relative to
the GAC/GTC class not associated with disease, the order of folding
stability is found to be CTG > GAC approximately = CAG > GTC for 10
repeats. Surprisingly, the folds formed by 30 repeats of CTG or CAG have no
higher melting temperature and are only 40% more stable in free energy than
those formed by 10 repeats. This finding suggests that triplet expansions
with higher repeat number may result from the formation of more folded
structures with similar stability rather than fewer but longer folds of
greater stability.
ARTICLES
Stability of intrastrand hairpin structures formed by the CAG/CTG class of DNA triplet repeats associated with neurological diseases
Department of Biological Sciences, Hedco Molecular Biology Laboratories, Molecular Biology Program, University of Southern California, Los Angeles, CA 90089-1340, USA.
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