DNA primase (PRIM) (PRIM)

DNA primase is a vital enzyme in eukaryotic DNA replication, responsible for synthesizing short RNA primers that provide the 3'-OH terminus required for DNA polymerases to begin synthesis (UniProt: P49642). It functions as a heterodimer consisting of a small catalytic subunit (PRIM1) and a large regulatory subunit (PRIM2), typically working in complex with DNA polymerase alpha (PubMed: 11440855). In the context of oncology, DNA primase is a significant target for nucleoside analogs like fludarabine. Fludarabine is converted intracellularly into its active metabolite, fludarabine triphosphate (F-ara-ATP), which potently inhibits primase activity by competing with ATP (PubMed: 2439135). This inhibition halts the initiation of Okazaki fragments on the lagging strand and primer synthesis on the leading strand, leading to DNA strand breaks and programmed cell death (PubMed: 8624760). Consequently, fludarabine is a cornerstone treatment for various hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (StatPearls: Fludarabine).

Other names

DNA-directed RNA polymerasePRIM1PRIM2p49/p58 complexDNA primase subunit 1DNA primase subunit 2DNA primase complex

Fludarabine triphosphate (F-ara-ATP) acts as a competitive inhibitor of DNA primase with respect to ATP, thereby blocking the synthesis of RNA primers necessary for the initiation of DNA replication (PubMed: 2439135).