Journal
BIOPOLYMERS
Volume 101, Issue 1, Pages 1-12Publisher
WILEY
DOI: 10.1002/bip.22236
Keywords
DNA loop structure; DNA thermodynamics; DNA stability; trinucleotide-repeat diseases; calorimetry; circular dichroism (CD)
Categories
Funding
- National Institutes of Health (NIH) [GM23509, GM34469, CA47995]
- Research Foundation (NRF) (Pretoria, RSA) [GUN 61103]
Ask authors/readers for more resources
Repetitive DNA sequences exhibit complex structural and energy landscapes, populated by metastable, noncanonical states, that favor expansion and deletion events correlated with disease phenotypes. To probe the origins of such genotype-phenotype linkages, we report the impact of sequence and repeat number on properties of (CNG) repeat bulge loops. We find the stability of duplexes with a repeat bulge loop is controlled by two opposing effects; a loop junction-dependent destabilization of the underlying double helix, and a self-structure dependent stabilization of the repeat bulge loop. For small bulge loops, destabilization of the underlying double helix overwhelms any favorable contribution from loop self-structure. As bulge loop size increases, the stabilizing loop structure contribution dominates. The role of sequence on repeat loop stability can be understood in terms of its impact on the opposing influences of junction formation and loop structure. The nature of the bulge loop affects the thermodynamics of these two contributions differently, resulting in unique differences in repeat size-dependent minima in the overall enthalpy, entropy, and free energy changes. Our results define factors that control repeat bulge loop formation; knowledge required to understand how this helix imperfection is linked to DNA expansion, deletion, and disease phenotypes. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 1-12, 2014.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available