A topoisomerase II cleavage site is associated with a novel mitochondrial DNA deletion

Hum Genet. 1995 Jan;95(1):75-81. doi: 10.1007/BF00225079.


Mitochondrial myopathies and encephalopathies can be caused by nucleotide substitutions, deletions or duplications of the mitochondrial DNA (mtDNA). In one such disorder, Kearns-Sayre Syndrome (KSS), large-scale heteroplasmic mtDNA deletions are often found. We describe a 14-year-old boy with clinical features of KSS, plus some additional features. Analysis of the entire mitochondrial genome by the polymerase chain reaction and Southern blotting revealed a 7864-bp mtDNA deletion, heteroplasmic in its tissue distribution. DNA sequencing established that the deletion was between nucleotides 6238 and 14,103, and flanked by a 4-bp (TCCT) direct repeat sequence. Deletions between direct repeats have been hypothesised to occur by a slipped-mismatching or illegitimate recombination event, or following the DNA cleavage action of topoisomerase II. Analysis of the gene sequence in the region surrounding the mtDNA deletion breakpoint in this patient revealed the presence of putative vertebrate topoisomerase II sites. We suggest that direct repeat sequences, together with putative topoisomerase II sites, may predispose certain regions of the mitochondrial genome to deletions.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Base Sequence
  • DNA
  • DNA Topoisomerases, Type II / metabolism
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Humans
  • Kearns-Sayre Syndrome / genetics*
  • Male
  • Molecular Sequence Data
  • Sequence Deletion*
  • Tissue Distribution


  • DNA, Mitochondrial
  • DNA
  • DNA Topoisomerases, Type II