Mechanisms of DNA Repeat Expansion

2007 ◽  
pp. 3-53 ◽  
Author(s):  
Richard R. Sinden ◽  
Malgorzata J. Pytlos ◽  
Vladimir N. Potaman
Keyword(s):  
Repeat Expansion ◽  
Dna Repeat

scholarly journals Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 702 ◽  
Author(s):  
Piergiorgio La Rosa ◽  
Sara Petrillo ◽  
Enrico Silvio Bertini ◽  
Fiorella Piemonte
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Protein Expression ◽  
Mitochondrial Dysfunction ◽  
Redox Homeostasis ◽  
Regulatory Region ◽  
Antioxidant Response ◽  
Repeat Expansion ◽  
Common Features ◽  
Dna Repeat

DNA repeat expansion disorders are a group of neuromuscular and neurodegenerative diseases that arise from the inheritance of long tracts of nucleotide repetitions, located in the regulatory region, introns, or inside the coding sequence of a gene. Although loss of protein expression and/or the gain of function of its transcribed mRNA or translated product represent the major pathogenic effect of these pathologies, mitochondrial dysfunction and imbalance in redox homeostasis are reported as common features in these disorders, deeply affecting their severity and progression. In this review, we examine the role that the redox imbalance plays in the pathological mechanisms of DNA expansion disorders and the recent advances on antioxidant treatments, particularly focusing on the expression and the activity of the transcription factor NRF2, the main cellular regulator of the antioxidant response.

scholarly journals Dynamic DNA Energy Landscapes and Substrate Complexity in Triplet Repeat Expansion and DNA Repair

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 709 ◽  
Author(s):  
Völker ◽  
Plum ◽  
Gindikin ◽  
Breslauer
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Repeat Expansion ◽  
Triplet Repeat ◽  
Energy Landscapes ◽  
Abasic Site ◽  
Triplet Repeat Expansion ◽  
Dna Repeat ◽  
Repeat Dna

DNA repeat domains implicated in DNA expansion diseases exhibit complex conformational and energy landscapes that impact biological outcomes. These landscapes include ensembles of entropically driven positional interchanges between isoenergetic, isomeric looped states referred to as rollamers. Here, we present evidence for the position-dependent impact on repeat DNA energy landscapes of an oxidative lesion (8oxodG) and of an abasic site analogue (tetrahydrofuran, F), the universal intermediate in base excision repair (BER). We demonstrate that these lesions modulate repeat bulge loop distributions within the wider dynamic rollamer triplet repeat landscapes. We showed that the presence of a lesion disrupts the energy degeneracy of the rollameric positional isomers. This lesion-induced disruption leads to the redistribution of loop isomers within the repeat loop rollamer ensemble, favoring those rollameric isomers where the lesion is positioned to be energetically least disruptive. These dynamic ensembles create a highly complex energy/conformational landscape of potential BER enzyme substrates to select for processing or to inhibit processing. We discuss the implications of such lesion-induced alterations in repeat DNA energy landscapes in the context of potential BER repair outcomes, thereby providing a biophysical basis for the intriguing in vivo observation of a linkage between pathogenic triplet repeat expansion and DNA repair.

CANVAS is a common form of late-onset hereditary ataxia

2020 ◽  
pp. 51-52
Author(s):  
Е.П. Нужный ◽  
Н.Ю. Абрамычева ◽  
Е.Г. Воробьева ◽  
Е.О. Иванова ◽  
Ю.А. Шпилюкова ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Clinical Picture ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Repeat Expansion ◽  
Hereditary Ataxia ◽  
Recessive Ataxia ◽  
Autosomal Recessive Ataxia

Синдром CANVAS (мозжечковая атаксия, невропатия и вестибулярная арефлексия) - аутосомно-рецессивная атаксия с поздним дебютом, обусловленная носительством биаллельной экспансии (AAGGG)n во 2-м интроне гена RFC1. До настоящего момента отсутствуют сведения о распространенности данного заболевания в российских семьях. Нами был проведен поиск биаллельной экспансии AAGGG-повторов у 35 российских пациентов с поздней мозжечковой атаксией. Верифицированы 5 пациентов (14,3%) с синдромом CANVAS и характерной клинической картиной. CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia) is a late-onset autosomal recessive ataxia due to biallelic (AAGGG)n repeat expansion in the 2nd intron of the RFC1 gene. There is no information on the CANVAS prevalence in Russian families. We searched for biallelic expansion of AAGGG repeats in 35 Russian patients with late-onset cerebellar ataxia. Five patients (14.3%) with CANVAS syndrome and a characteristic clinical picture were verified.

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