The generation of mitochondrial DNA large-scale deletions in human cells

Abstract

Large-scale deletions of human mitochondrial DNA (mtDNA) are a common cause of mitochondrial diseases. In order to prevent and treat these mitochondrial diseases, it is important and necessary to understand the mechanisms behind the generation of these deletions. Generally, there exist three kinds of large-scale deletions: deletions almost occur within two direct repeats with identical sequences (class I deletions), deletions are flanked by imperfect repeats (class II deletions) and by no direct repeats (class III deletions). Two major hypotheses are suggested to generate these deletions: replication for class I/II deletions through slipped mispairing between two repeats, and repair mainly for class II/III deletions mediated by mtDNA double-strand breaks. It seems possible that these two mechanisms work together as a powerful and complementary system to compensate for their defects in the generation of all these deletions, not respectively. © 2011 The Japan Society of Human Genetics All rights reserved.