Yingquan Yang, Yang Wang, Zhenzhen Yan, Zhigang Li, Pei Guo
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引用次数: 0
摘要
肌营养不良症 2 型(DM2)是一种神经退行性疾病,由细胞核酸结合蛋白(CNBP)基因内含子 1 中的辛酸/癸酸甘油三酯(CCTG)四核苷酸重复扩增引起。由 CCTG 重复序列形成的非 B DNA 结构会导致基因不稳定,而 CCTG 重复序列中的 NCTG(N = A/T/G)中断基序则有助于保持基因组的稳定性。然而,中断基序是否会影响 CCTG 重复序列的 DNA 结构仍不清楚。在这里,我们报告了四个带有3'-A/T/G中断残基的CCTG重复序列形成哑铃状结构,而不带3'-C中断残基的CCTG重复序列则形成多环结构,这种多环结构具有构象动力学特性,可能会导致CCTG重复序列更容易摆脱DNA错配修复并导致重复序列扩展。这些结果为了解 DM2 中 CCTG 重复序列的遗传不稳定性提供了新的结构见解。
Effects of interrupting residues on DNA dumbbell structures formed by CCTG tetranucleotide repeats associated with myotonic dystrophy type 2
Myotonic dystrophy type 2 (DM2) is a neurogenerative disease caused by caprylic/capric triglyceride (CCTG) tetranucleotide repeat expansions in intron 1 of the cellular nucleic acid-binding protein (CNBP) gene. Non-B DNA structures formed by CCTG repeats can promote genetic instability, whereas interrupting motifs of NCTG (N = A/T/G) within CCTG repeats help to maintain genomic stability. However, whether the interrupting motifs can affect DNA structures of CCTG repeats remains unclear. Here, we report that four CCTG repeats with an interrupting 3′-A/T/G residue formed dumbbell structures, whereas a non-interrupting 3′-C residue resulted in a multi-loop structure exhibiting conformational dynamics that may contribute to a higher tendency of escaping from DNA mismatch repair and causing repeat expansions. The results provide new structural insights into the genetic instability of CCTG repeats in DM2.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.