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Title: Thermodynamic analysis of DNA hybridization signatures near mitochondrial DNA deletion breakpoints
Authors: Lakshmanan, Lakshmi Narayanan
Yee, Zhuangli
Halliwell, Barry
Gruber, Jan
Gunawan, Rudiyanto
Keywords: Science::Medicine
Issue Date: 2021
Source: Lakshmanan, L. N., Yee, Z., Halliwell, B., Gruber, J. & Gunawan, R. (2021). Thermodynamic analysis of DNA hybridization signatures near mitochondrial DNA deletion breakpoints. IScience, 24(3), 102138-.
Journal: iScience 
Abstract: 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.
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.102138
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National University of Singapore
Rights: © 2021 The Authors. This is an open access article under the CC BY license
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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