InterPro domain: IPR034154

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in archaeal DnaG-type primases and in mitochondrial twinkle helicase. In archaea, DnaG is tightly associated with the RNA-degrading exosome [ 1 , 2 ]. DnaG of Sulfolobus solfataricus has been shown to exhibit primase activity in vitro [ 3 ]. Twinkle is needed for mitochondrial DNA replication and may be involved in recombinational repair of mitochondrial DNA [ 4 ].

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). This glutamate and two aspartates, cluster together to form a highly acid surface patch. The conserved glutamate may act as a general base in nucleotide polymerization by primases. The DXD motif may co-ordinate Mg ²⁺ , a cofactor required for full catalytic function [ 5 ].

1. Structure and function of the archaeal exosome. Wiley Interdiscip Rev RNA 5, 623-35
2. The archaeal DnaG protein needs Csl4 for binding to the exosome and enhances its interaction with adenine-rich RNAs. RNA Biol 10, 415-24
3. Characterization of a functional DnaG-type primase in archaea: implications for a dual-primase system. J. Mol. Biol. 397, 664-76
4. Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE. Nucleic Acids Res. 44, 4200-10
5. Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res. 26, 4205-13