Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region

Carlos T. Moraes, Francesca Andreetta, Eduardo Bonilla, Sara Shanske, Salvatore DiMauro, Eric A. Schon

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We identified two patients with progressive external ophthalmoplegia, a mitochondrial disease, who harbored a population of partially deleted mitochondrial DNA (mtDNA) with unusual properties. These molecules were deleted from mtDNA positions 548 to 4,442 and encompassed not only rRNA sequences but the heavy-strand promoter region as well. A 13-bp direct repeat was found flanking the breakpoint precisely, with the repeat at positions 535 to 547 located within the binding site for mitochondrial transcription factor 1 (mtTF1). This is the second mtDNA deletion involving a 13-bp direct repeat reported but is at least 10 times less frequent in the patient population than the former one. In situ hybridization studies showed that transcripts under the control of the light-strand promoter were abundant in muscle fibers with abnormal proliferation of mitochondria, while transcripts directed by the heavy-strand promoter, whether of genes residing inside or outside the deleted region, were not. The efficient transcription from the light-strand promoter implies that the major heavy- and light-strand promoters, although physically close, are functionally independent, confirming previous in vitro studies.

Original languageEnglish
Pages (from-to)1631-1637
Number of pages7
JournalMolecular and Cellular Biology
Issue number3
Publication statusPublished - Mar 1991

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology


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