Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA

Shuji Mita, Rosario Rizzuto, Carlos T. Moraes, Sara Shanske, Enrica Arnaudo, Gian Maria Fabrizi, Yasutoshi Koga, Salvatore Dimauro, Eric A. Schon

Research output: Contribution to journalArticle

302 Scopus citations

Abstract

Large-scale deletions of mitochondrial DNA (mtDNA) have been described in patients with progressive external ophthalmoplegia (PEO) and ragged red fibers. We have determined the exact deletion breakpoint in 28 cases with PEO, including 12 patients already shown to harbor an identical deletion; the other patients had 16 different deletions. The deletions fell into two classes. In Class I (9 deletions; 71% of the patients), the deletion was flanked by perfect direct repeats, located (in normal mtDNA) at the edges of the deletion. In Class II (8 deletions; 29% of patients), the deletions were not flanked by any obviously unique repeat element, or they were flanked by repeat elements which were located imprecisely relative to the breakpoints. Computer analysis showed a correlation between the location of the deletion breakpoints and sequences in human mtDNA similar to the target sequence for Drosophila topoisomerase II. It is not known how these deletions originate, but both slipped mispairing and legitimate recombination could be mechanisms playing a major role in the generation of the large mtDNA deletions found in PEO.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalNucleic acids research
Volume18
Issue number3
DOIs
StatePublished - Feb 11 1990

ASJC Scopus subject areas

  • Genetics

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