دورية أكاديمية
أعرض في EDS

Frustration Between Preferred States of Complementary Trinucleotide Repeat DNA Hairpins Anticorrelates with Expansion Disease Propensity.

التفاصيل البيبلوغرافية
العنوان: Frustration Between Preferred States of Complementary Trinucleotide Repeat DNA Hairpins Anticorrelates with Expansion Disease Propensity.
المؤلفون: Xu P; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA. Electronic address: https://twitter.com/@XPengning., Zhang J; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA., Pan F; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA., Mahn C; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA., Roland C; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA., Sagui C; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA. Electronic address: sagui@ncsu.edu., Weninger K; Department of Physics, North Carolina State University, Raleigh, NC 27695, USA. Electronic address: keith.weninger@ncsu.edu.
المصدر: Journal of molecular biology [J Mol Biol] 2023 May 15; Vol. 435 (10), pp. 168086. Date of Electronic Publication: 2023 Apr 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: DNA*/genetics , DNA*/chemistry , Trinucleotide Repeats* , Neurodegenerative Diseases*/genetics, Humans ; DNA, Complementary ; Nucleic Acid Conformation ; Trinucleotide Repeat Expansion/genetics
مستخلص: DNA trinucleotide repeat (TRs) expansion beyond a threshold often results in human neurodegenerative diseases. The mechanisms causing expansions remain unknown, although the tendency of TR ssDNA to self-associate into hairpins that slip along their length is widely presumed related. Here we apply single molecule FRET (smFRET) experiments and molecular dynamics simulations to determine conformational stabilities and slipping dynamics for CAG, CTG, GAC and GTC hairpins. Tetraloops are favored in CAG (89%), CTG (89%) and GTC (69%) while GAC favors triloops. We also determined that TTG interrupts near the loop in the CTG hairpin stabilize the hairpin against slipping. The different loop stabilities have implications for intermediate structures that may form when TR-containing duplex DNA opens. Opposing hairpins in the (CAG) ∙ (CTG) duplex would have matched stability whereas opposing hairpins in a (GAC) ∙ (GTC) duplex would have unmatched stability, introducing frustration in the (GAC) ∙ (GTC) opposing hairpins that could encourage their resolution to duplex DNA more rapidly than in (CAG) ∙ (CTG) structures. Given that the CAG and CTG TR can undergo large, disease-related expansion whereas the GAC and GTC sequences do not, these stability differences can inform and constrain models of expansion mechanisms of TR regions.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
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معلومات مُعتمدة: R01 GM118508 United States GM NIGMS NIH HHS; R01 GM132263 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Huntington's disease; hairpin slippage; kinetics; molecular dynamics; single molecule FRET; trinucleotide interrupts
المشرفين على المادة: 9007-49-2 (DNA)
0 (DNA, Complementary)
تواريخ الأحداث: Date Created: 20230406 Date Completed: 20230525 Latest Revision: 20240516
رمز التحديث: 20240516
مُعرف محوري في PubMed: PMC10191799
DOI: 10.1016/j.jmb.2023.168086
PMID: 37024008
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2023.168086