DNA polymerase alpha-primase complex (Pol-prim) (Pol-prim)

The DNA polymerase alpha-primase complex is a fundamental enzymatic assembly required for the initiation of DNA replication in eukaryotic cells (UniProt P09884, P49642). It is composed of four subunits: two primase subunits (PRIM1 and PRIM2) that synthesize a short RNA primer, and two polymerase subunits (POLA1 and POLA2) that extend the primer with deoxyribonucleotides (PMID: 26826117). This complex is unique because it is the only enzyme capable of starting DNA synthesis de novo on a template, making it indispensable for both leading and lagging strand synthesis (NCBI: DNA Replication). In clinical practice, this complex and its viral homologs are major therapeutic targets. Anticancer drugs like cytarabine and gemcitabine act as antimetabolites that inhibit the polymerase activity, while antiviral agents like acyclovir selectively target viral DNA polymerases to halt infection (StatPearls: DNA Polymerase Inhibitors). Because these enzymes are central to genomic stability and cell division, they remain a primary focus for developing treatments against hyperproliferative diseases and viral pathogens.

Other names

DNA polymerase alphaDNA primasePol alpha-primaseDNA-directed DNA polymerase alphaDNA-directed RNA polymerase (primase)DNA polymerases and DNA primase

Inhibition of DNA synthesis via competitive inhibition of dNTP binding or incorporation into DNA leading to chain termination.