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The Influence of Sequence Context and Length on the Kinetics of DNA Duplex Formation from Complementary Hairpins Possessing (CNG) Repeats
journal contribution
posted on 2005-04-20, 00:00 authored by Anthony M. Paiva, Richard D. SheardyThe formation of unusual structures during DNA replication has been invoked for gene expansion
in genomes possessing triplet repeat sequences, CNG, where N = A, C, G, or T. In particular, it has been
suggested that the daughter strand of the leading strand partially dissociates from the parent strand and
forms a hairpin. The equilibrium between the fully duplexed parent:daugter species and the parent:hairpin
species is dependent upon their relative stabilities and the rates of reannealing of the daughter strand
back to the parent. These stabilities and rates are ultimately influenced by the sequence context of the
DNA and its length. Previous work has demonstrated that longer strands are more stable than shorter
strands and that the identity of N also influences the thermal stability [Paiva, A. M.; Sheardy, R. D.
Biochemistry 2004, 43, 14218−14227]. Here, we show that the rate of duplex formation from complementary
hairpins is also sequence context and length dependent. In particular, longer duplexes have higher activation
energies than shorter duplexes of the same sequence context. Further, [(CCG):(GGC)] duplexes have
lower activation energies than corresponding [(CAG):(GTC)] duplexes of the same length. Hence, hairpins
formed from long CNG sequences are more thermodynamically stable and have slower kinetics for
reannealing to their complement than shorter analogues. Gene expansion can now be explained in terms
of thermodynamics and kinetics.