Effects of interrupting residues on DNA dumbbell structures formed by CCTG tetranucleotide repeats associated with myotonic dystrophy type 2

Author:

Yang Yingquan12,Wang Yang23,Yan Zhenzhen12,Li Zhigang1ORCID,Guo Pei2ORCID

Affiliation:

1. School of Biology and Biological Engineering South China University of Technology Guangzhou China

2. Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences China

3. School of Materials Science and Engineering Tianjin University China

Abstract

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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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