Target intelligence / Profile preview

DNA polymerase alpha-associated DNA primase (Pol α-primase)

Target
Pol α-primase
Molecular classification
Enzyme, DNA polymerase, Primase
01

Overview

DNA polymerase alpha-associated DNA primase (Pol α-primase) is a multi-subunit enzyme complex essential for the initiation of eukaryotic DNA replication. It consists of the catalytic and regulatory subunits of DNA polymerase alpha (POLA1 and POLA2) and two primase subunits (PRIM1 and PRIM2). The complex is uniquely responsible for synthesizing short RNA-DNA primers that are subsequently elongated by high-fidelity polymerases delta and epsilon during S-phase. Due to its central role in cell proliferation, Pol α-primase is a major therapeutic target for anticancer agents, particularly nucleoside analogs like cytarabine and gemcitabine, which inhibit DNA synthesis and trigger apoptosis in rapidly dividing cells. Additionally, viral DNA polymerases with analogous functions are critical targets for antiviral therapies used to treat infections such as Hepatitis B and Herpes simplex virus.

Other names
DNA polymerase alpha complexPol alpha-primaseDNA polymerase-associated DNA primaseDNA polymerase-associated protein 1PDAP1HASPP28
02

Mechanism of action

Inhibition of DNA synthesis through competitive inhibition of dNTP binding or chain termination following incorporation into the growing DNA strand.

03

Biological functions

DNA replicationRNA primer synthesisCell cycle regulation
04

Disease associations

CancerViral infectionAutoimmune disease
05

Safety considerations

MyelosuppressionGastrointestinal toxicityNephrotoxicityNeurotoxicity
06

Interacting drugs

Cytarabine

5 more in the full profile.

07

Biomarkers

POLA1 expressionKi-67 proliferation index

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