Dataset Information

Structure of even/odd trinucleotide repeat sequences modulates persistence of non-B conformations and conversion to duplex.

ABSTRACT: Expansion of trinucleotide repeats (TNR) has been implicated in the emergence of neurodegenerative diseases. Formation of non-B conformations such as hairpins by these repeat sequences during DNA replication and/or repair has been proposed as a contributing factor to expansion. In this work we employed a combination of fluorescence, chemical probing, optical melting, and gel shift assays to characterize the structure of a series of (CTG)(n) sequences and the kinetic parameters describing their interaction with a complementary sequence. Our structure-based experiments using chemical probing reveal that sequences containing an even or odd number of CTG repeats adopt stem-loop hairpins that differ from one another by the absence or presence of a stem overhang. Furthermore, we find that this structural difference dictates the rate at which the TNR hairpins convert to duplex with a complementary CAG sequence. Indeed, the rate constant describing conversion to (CAG)(10)/(CTG)(n) duplex is slower for sequences containing an even number of CTG repeats than for sequences containing an odd number of repeats. Thus, when both the CAG and CTG hairpins have an even number of the repeats, they display a longer lifetime relative to when the CTG hairpin has an odd number of repeats. The difference in lifetimes observed for these TNR hairpins has implications toward their persistence during DNA replication or repair events and could influence their predisposition toward expansion. Taken together, these results contribute to our understanding of trinucleotide repeats and the factors that regulate persistence of hairpins in these repetitive sequences and conversion to canonical duplex.

SUBMITTER: Figueroa AA

PROVIDER: S-EPMC3101280 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Structure of even/odd trinucleotide repeat sequences modulates persistence of non-B conformations and conversion to duplex.

Figueroa Amalia Avila AA Cattie Douglas D Delaney Sarah S

Biochemistry 20110504 21

Expansion of trinucleotide repeats (TNR) has been implicated in the emergence of neurodegenerative diseases. Formation of non-B conformations such as hairpins by these repeat sequences during DNA replication and/or repair has been proposed as a contributing factor to expansion. In this work we employed a combination of fluorescence, chemical probing, optical melting, and gel shift assays to characterize the structure of a series of (CTG)(n) sequences and the kinetic parameters describing their i ...[more]

PMID: 21526744

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Project description:Numerical categories such as parity, i.e., being odd or even, have frequently been shown to influence how particular numbers are processed. Mathematically, number parity is defined categorically. So far, cognitive, and psychological accounts have followed the mathematical definition and defined parity as a categorical psychological representation as well. In this manuscript, we wish to test the alternative account that cognitively, parity is represented in a more gradual manner such that some numbers are represented as "more odd" or "more even" than other odd or even numbers, respectively. Specifically, parity processing might be influenced by more specific properties such as whether a number is a prime, a square number, a power of 2, part of a multiplication table, divisible by 4 or by 5, and many others. We suggest that these properties can influence the psychologically represented parity of a number, making it more or less prototypical for odd- or evenness. In the present study, we tested the influence of these numerical properties in a bimanual parity judgment task with auditorily presented two-digit numbers. Additionally, we further investigated the interaction of these numerical properties with linguistic factors in three language groups (English, German, and Polish). Results show significant effects on reaction times of the congruity of parity status between decade and unit digits, even if numerical magnitude and word frequency are controlled. We also observed other effects of the above specific numerical properties, such as multiplication attributes, which facilitated or interfered with the speed of parity judgment. Based on these effects of specific numerical properties we proposed and elaborated a parity continuum account. However, our cross-lingual study also suggests that parity representation and/or access seem to depend on the linguistic properties of the respective language or education and culture. Overall, the results suggest that the "perceived" parity is not the same as objective parity, and some numbers are more prototypical exemplars of their categories.

Dataset Information

Structure of even/odd trinucleotide repeat sequences modulates persistence of non-B conformations and conversion to duplex.

Publications

Structure of even/odd trinucleotide repeat sequences modulates persistence of non-B conformations and conversion to duplex.

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