Context dependence of trinucleotide repeat structures
ACS Citation
Degtyareva, N. N.; Barber, C. A.; Sengupta, B.; Petty, J. T. Context dependence of trinucleotide repeat structures. Biochemistry 2010, 49, 3024-30.
Version of Record
Abstract
Long repeated sequences of DNA and their associated secondary structure govern the development and severity of a significant class of neurological diseases. Utilizing the effect of base stacking on fluorescence quantum yield, 2-aminopurine substitutions for adenine previously demonstrated sequestered bases in the stem and exposed bases in the loop for an isolated (CAG)(8) sequence. This study evaluates (CAG)(8) that is incorporated into a duplex, as this three-way junction is a relevant model for intermediates that lead to repeat expansion during DNA replication and repair. From an energetic perspective, thermally induced denaturation indicates that the duplex arms dictate stability and that the secondary structure of the repeated sequence is disrupted. Substitutions with 2-aminopurine probe base exposure throughout this structure, and two conclusions about secondary structure are derived. First, the central region of (CAG)(8) is more solvent-exposed than single-stranded DNA, which suggests that hairpin formation in the repeated sequence is disrupted. Second, base stacking becomes compromised in the transition from the duplex to (CAG)(8), resulting in bases that are most similar to single-stranded DNA at the junction. Thus, an open (CAG)(8) loop and exposed bases in the arms indicate that the strand junction profoundly influences repeated sequences within three-way junctions.
Source Name
Biochemistry
Publication Date
1-1-2010
Volume
49
Issue
14
Page(s)
646-655
Document Type
Citation
Citation Type
Article