Action of mitochondrial endonuclease G on DNA damaged by L-ascorbic acid, peplomycin, and cis-diamminedichloroplatinum (II).

Mitochondrial DNA (mtDNA) suffers extensive damage from the environment, however, the enzymes involved in the repair of mtDNA are still unknown. Here, we partially purified mitochondrial endonuclease G (Endo G) from the bovine heart, and examined the action of Endo G on damaged DNA. Treatment of DNA with L-ascorbic acid or peplomycin, that introduces single-strand breaks through active oxygen radicals, greatly enhanced the susceptibility to nucleolytic attacks from Endo G. The enzyme cleaved at or near sites where single-strand breaks were present in the opposite strand. Cisplatin-mediated DNA damage, which causes intrastrand crosslinks between adjacent guanine residues, also facilitated Endo G digestion, indicating that the enzyme can recognize local distortions in the duplex DNA introduced by adducts. These nucleolytic properties of Endo G in vitro suggest its possible involvement in the maintenance of mtDNA by eliminating defective genomes from the multicopy pool.