Primers for Mitochondrial DNA Replication Generated by Endonuclease G

Abstract

Endonuclease G (Endo G) is widely distributed among animals and cleaves DNA at double-stranded (dG)n.(dC)n and at single-stranded (dC)n tracts. Endo G is synthesized as a propeptide with an amino-terminal presequence that targets the nuclease to mitochondria. Endo G can also be detected in extranucleolar chromatin. In addition to deoxyribonuclease activities, Endo G also has ribonuclease (RNase) and RNase H activities and specifically cleaves mouse mitochondrial RNA and DNA-RNA substrates containing the origin of heavy-strand DNA replication (OH). The cleavage sites match those found in vivo, indicating that Endo G is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA.