Ribonucleotide reductase, DNA polymerase alpha, and DNA primase (RNR, Pol α, and Primase)

Ribonucleotide reductase, DNA polymerase alpha, and DNA primase are three essential enzymes that coordinate the initiation and elongation phases of DNA replication in eukaryotic cells. Ribonucleotide reductase generates the deoxyribonucleotide building blocks needed for DNA synthesis by converting ribonucleotides to deoxyribonucleotides via a radical-based mechanism. DNA primase synthesizes short RNA primers on the DNA template, which are subsequently elongated by DNA polymerase alpha, forming short RNA-DNA fragments that prime DNA synthesis on both leading and lagging strands. These enzymes are highly regulated, interact physically in some multi-protein complexes, and are therapeutic targets in cancer and infectious diseases due to their critical role in DNA replication and cell proliferation.

Other names

RNRribonucleoside diphosphate reductasePol αpolymerase-alphaDNA-dependent RNA polymerase

Inhibitors targeting these enzymes employ diverse mechanisms to disrupt DNA synthesis. Ribonucleotide reductase inhibitors block de novo dNTP synthesis, thereby inhibiting DNA replication and inducing cytotoxicity in rapidly dividing cells. DNA polymerase alpha inhibitors impair the initiation of DNA synthesis and stall replication fork progression. Primase inhibitors prevent the formation of essential RNA primers, ultimately blocking DNA replication.