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© Research
Publication : PloS one

An appraisal of human mitochondrial DNA instability: new insights into the role of non-canonical DNA structures and sequence motifs

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 29 Mar 2013

Oliveira PH, da Silva CL, Cabral JM

Link to Pubmed [PMID] – 23555828

PLoS ONE 2013;8(3):e59907

Mitochondrial DNA (mtDNA) deletion mutations are frequently observed in aged postmitotic tissues and are the cause of a wide range of human disorders. Presently, the molecular bases underlying mtDNA deletion formation remain a matter of intense debate, and it is commonly accepted that several mechanisms contribute to the spectra of mutations in the mitochondrial genome. In this work we performed an extensive screening of human mtDNA deletions and evaluated the association between breakpoint density and presence of non-canonical DNA elements and over-represented sequence motifs. Our observations support the involvement of helix-distorting intrinsically curved regions and long G-tetrads in eliciting instability events. In addition, higher breakpoint densities were consistently observed within GC-skewed regions and in the close vicinity of the degenerate sequence motif YMMYMNNMMHM. A parallelism is also established with hot spot motifs previously identified in the nuclear genome, as well as with the minimal binding site for the mitochondrial transcription termination factor mTERF. This study extends the current knowledge on the mechanisms driving mitochondrial rearrangements and opens up exciting avenues for further research.

http://www.ncbi.nlm.nih.gov/pubmed/23555828