Large-scale deletions of mitochondrial DNA (mtDNA) are common events that have been found to occur in human ageing and in patients with mitochondrial myopathies. The mechanisms by which these deletions occur remain unclear, but several mechanisms have been proposed, such as slipped-mispairing, illegitimate recombination, and oxidative reactions elicited by free radicals. In addition, the DNA topological stress and local DNA structures have been suggested as the important factors in eliciting the recombinational events. Upon examination of 128 breakpoints of human mtDNA deletions that have been published in the past 8 years, we found that these large-scale deletions often occur at some ‘hot-regions’. We thus hypothesized that there exist unusual structures in these regions of human mtDNA that are important for eliciting the deletions. To test this hypothesis, we used PCR techniques to amplify the sequences of the so-called hot-regions and analysed the PCR products by two-dimensional gel electrophoresis. We found that the sequences of nucleotide position (np) 5221–5988, np 6928–7493, np 7901–8732 and np 15327–16228 exhibited retarded mobilities like bent DNA structures; np 5989–6750, np 13282–13653 and np 13282–14850 showed increased mobilities like anti-bent DNA structures. Moreover, except for the sequences of np 1175–1766 found in 12 S and 16 S rRNA genes exhibiting abnormal mobility like bent DNA structures, we did not observe significant mobility abnormalities in the np 499–5545 region where deletions rarely occurred. We thus conclude that these hot-regions assume some kinds of unusual DNA structures, which may render these regions more sensitive to the attack of free radicals or serve as recognition motifs for certain recombination machinery that is involved in the large-scale deletions of human mtDNA.
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Research Article|
September 15 1996
The unusual structures of the hot-regions flanking large-scale deletions in human mitochondrial DNA
Jeng-Horng HOU;
Jeng-Horng HOU
1Department of Biochemistry, and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China
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Yau-Huei WEI
Yau-Huei WEI
*
1Department of Biochemistry, and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China
*To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
January 29 1996
Revision Received:
May 07 1996
Accepted:
May 14 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (3): 1065–1070.
Article history
Received:
January 29 1996
Revision Received:
May 07 1996
Accepted:
May 14 1996
Citation
Jeng-Horng HOU, Yau-Huei WEI; The unusual structures of the hot-regions flanking large-scale deletions in human mitochondrial DNA. Biochem J 15 September 1996; 318 (3): 1065–1070. doi: https://doi.org/10.1042/bj3181065
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