Mechanism of <i>numt</i> insertion.

<p>Mitochondrial DNA has been suggested to get into the nucleus via a few different pathways. (A) The most supported pathway so far involve the degradation of abnormal mitochondria <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000834#pgen.1000834-Campbell1" target="_blank">[53]</a>. Several <i>yme</i> (yeast mitochondrial escape) strains show high level of DNA escape to the nucleus. <i>yme1</i> mutant cause the inactivation of YMe1p protein, a mitochondrial-localized ATP-dependent metallo-protease leading to high escape rate of mtDNA to the nucleus. Mitochondria of <i>yme1</i> strain are taken up for degradation by the vacuole more frequently than the wild-type strain. Other pathways to get mitochondrial DNA into the nucleus were suggested including: (B) lysis of mitochondrial compartment, (C) encapsulation of mitochondrial DNA inside the nucleus, (D) direct physical association between the mitochondria and the nucleus and membrane fusions. (E) Mitochondrial DNA that enters the nucleus can integrate into nuclear chromosomes. mtDNA integrated into the chromosome during the repair of DSBs in a mechanism known as non-homologous end-joining (NHEJ). The insertion involves two DSB repair events. Each can be repaired with or without the involvement of short microhomology. In microhomology-mediated NHEJ, base-pair complements are available between the <i>numt</i> and the chromosome ends, similar to the sticky ends created by restriction enzymes.