Primers for Mitochondrial DNA Replication Generated by Endonuclease G

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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 (O H ). The cleavage sites match those found in vivo, indicating that Endo G is capable of generating the RNA primers required by DNA polymerase γ to initiate replication of mitochondrial DNA.