DNA primase subunit 1 (PRIM1)

DNA primase subunit 1 (PRIM1) is the small, catalytic subunit of the eukaryotic DNA primase complex, forming a heterodimer with the large PRIM2 subunit and assembling with DNA polymerase alpha in a heterotetrameric primase–polymerase complex[1][2][3][5]. PRIM1's function is to synthesize short RNA primers on single-stranded DNA templates during the initiation of DNA replication, enabling extension by DNA polymerases and accurate duplication of cellular genomes[1][2][4][5]. Its activity is crucial during the S-phase of the cell cycle for the formation of Okazaki fragments in lagging strand synthesis and the overall fidelity and stability of chromosomal replication. Increased PRIM1 expression has been linked to cancer progression, and loss-of-function mutations can result in severe developmental disorders marked by dwarfism, immune deficiency, and lipodystrophy[1][3]. While not yet a direct clinical drug target, experimental research explores synthetic lethality in DNA damage response–deficient tumors through PRIM1 inhibition[3].

Other names

DNA primase small subunitPRIM1p49DNA primase 49 kDa subunitPDILDNA primase subunit 48Primase (DNA) subunit 1Primase p49 subunitPrimase polypeptide 149 kDaPrimase, DNA, polypeptide 1 (49 kDa)

Experimental inhibition of PRIM1 (e.g., via siRNA or synthetic lethality) impairs DNA synthesis, halts tumor cell proliferation, and can induce apoptosis. As part of DNA replication machinery, blockade leads to replication stress and cell death in susceptible, repair-deficient cells.