Evidence map›Paper›PMID 22100810›Full record

ArticleBiochemical and biophysical research communications2011

Premutation huntingtin allele adopts a non-B conformation and contains a hot spot for DNA damage.

Daniel A Jarem, Sarah Delaney

Abstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Daniel A JaremDepartment of Chemistry, Brown University, Providence, RI 02912, USA.
Sarah Delaney

Funding

Inflammation as a Mediator of Dynamic DNA MutationsR01ES019296 · NIEHS · BROWN UNIVERSITY · PI DELANEY, SARAH · 2010 to 2014
$2.2M
NIEHS NIH HHS ES019296NIEHS NIH HHS R01 ES019296
6 · The paper itself

Abstract

The expansion of a CAG trinucleotide repeat (TNR) sequence has been linked to several neurological disorders, for example, Huntington's disease (HD). In HD, healthy individuals have 5-35 CAG repeats. Those with 36-39 repeats have the premutation allele, which is known to be prone to expansion. In the disease state, greater than 40 repeats are present. Interestingly, the formation of non-B DNA conformations by the TNR sequence is proposed to contribute to the expansion. Here we provide the first structural and thermodynamic analysis of a premutation length TNR sequence. Using chemical probes of nucleobase accessibility, we found that similar to (CAG)(10), the premutation length sequence (CAG)(36) forms a stem-loop hairpin and contains a hot spot for DNA damage. Additionally, calorimetric analysis of a series of (CAG)(n) sequences, that includes repeat tracts in both the healthy and premutation ranges, reveal that thermodynamic stability increases linearly with the number of repeats. Based on these data, we propose that while non-B conformations can be formed by TNR tracts found in both the healthy and premutation allele, only sequences containing at least 36 repeats have sufficient thermodynamic stability to contribute to expansion.

Indexed as

DNA DamageNucleic Acid ConformationTrinucleotide RepeatsAllelesCalorimetryDNA, B-FormHumansHuntingtin ProteinHuntington DiseaseMutationNerve Tissue ProteinsNuclear ProteinsPeroxynitrous AcidTransition TemperatureDNA, B-FormHTT protein, humanHuntingtin ProteinNerve Tissue ProteinsNuclear ProteinsPeroxynitrous Acid

Identifiers

PMID22100810
PMCPMC3237924

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.