Thermodynamic analysis of DNA hybridization signatures near mitochondrial DNA deletion breakpoints

iScience

Zhuangli Yee¹  Rudiyanto Gunawan²  Jan Gruber²  Barry Halliwell³  Lakshmi Narayanan Lakshmanan⁴ 

[1] Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland;Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore;Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore;

关键词: Molecular Genetics;    Bioinformatics;    Sequence Analysis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Broad evidence in the literature supports double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. While DNA misalignment during DSB repair is commonly proposed as the mechanism by which DSBs cause deletion mutations, details such as the specific DNA repair errors are still lacking. Here, we used DNA hybridization thermodynamics to infer the sequence lengths of mtDNA misalignments that are associated with mtDNA deletions. We gathered and analyzed 9,921 previously reported mtDNA deletion breakpoints in human, rhesus monkey, mouse, rat, and Caenorhabditis elegans. Our analysis shows that a large fraction of mtDNA breakpoint positions can be explained by the thermodynamics of short ≤ 5-nt misalignments. The significance of short DNA misalignments supports an important role for erroneous non-homologous and micro-homology-dependent DSB repair in mtDNA deletion formation. The consistency of the results of our analysis across species further suggests a shared mode of mtDNA deletion mutagenesis.

【 授权许可】

Unknown