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Trinucleotide repeat DNA alters structure to minimize the thermodynamic impact of 8-oxo-7,8-dihydroguanine.


ABSTRACT: In the phenomenon of trinucleotide repeat (TNR) expansion, an important interplay exists between DNA damage repair of 8-oxo-7,8-dihydroguanine (8-oxoG) and noncanonical structure formation. We show that TNR DNA adapts its structure to accommodate 8-oxoG. Using chemical probe analysis, we find that CAG repeats composing the stem-loop arm of a three-way junction alter the population of structures in response to 8-oxoG by positioning the lesion at or near the loop. Furthermore, we find that oligonucleotides composed of odd-numbered repeat sequences, which form populations of two structures, will also alter their structure to place 8-oxoG in the loop. However, sequences with an even number of repeats do not display this behavior. Analysis by differential scanning calorimetry indicates that whe

SUBMITTER: Volle CB 

PROVIDER: S-EPMC3254800 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature