DNA primase and related DNA replication initiation complexes (Pol-Prim)

DNA primase is a specialized RNA polymerase that is essential for the initiation of DNA replication across all domains of life. Because DNA polymerases are unable to synthesize DNA de novo, primase creates short RNA primers (or RNA-DNA hybrids in eukaryotes) that provide the necessary 3-hydroxyl group for elongation by replicative polymerases. In eukaryotic cells, primase exists as a heterodimer of PRIM1 and PRIM2 subunits, which functions in a stable complex with DNA polymerase alpha (the Pol-Prim complex) to initiate both leading-strand synthesis and the production of Okazaki fragments on the lagging strand. This complex is a critical therapeutic target in oncology, as its inhibition halts the cell cycle and induces apoptosis in rapidly dividing cancer cells. Furthermore, structural differences between human primase and the primases of bacteria (DnaG) or viruses (such as the HSV helicase-primase complex) allow for the development of selective antimicrobial and antiviral agents that disrupt pathogen replication without affecting the host.

Other names

DNA polymerase alpha-primase complexRNA primaseDnaGPRIM1-PRIM2 complexPrimosomeDNA-directed RNA polymerase (EC 2.7.7.6)

Inhibition of RNA primer synthesis, competitive inhibition of nucleotide incorporation into the primer-template junction, and disruption of the physical interaction between helicase and primase subunits, leading to replication fork arrest.