Primase

Archaeal and eukaryote primases are heterodimeric proteins with one large regulatory and one minuscule catalytic subunit.

[4] The central subdomain forms a toprim fold which is made of a mixture five beta sheets and six alpha helices.

[12] This classification also emphasizes the broad origins of AEP primases; the superfamily is now recognized as transitioning between RNA and DNA functions.

For example, removing the part corresponding to the large subunit in a fusion protein PolpTN2 results in a slower enzyme with reverse transcriptase activity.

[16][11] Primases with terminal transferase functionality are capable of adding nucleotides to the 3’ end of a DNA strand independently of a template.

[17] Human PrimPol (ccdc111[16]) serves both primase and polymerase functions, like many archaeal primases; exhibits terminal transferase activity in the presence of manganese; and plays a significant role in translesion synthesis[18] and in restarting stalled replication forks.

PrimPol is actively recruited to damaged sites through its interaction with RPA, an adapter protein that facilitates DNA replication and repair.

[18] Unlike most primases, PrimPol is uniquely capable of starting DNA chains with dNTPs.

[16] PriS, the archaeal primase small subunit, has a role in translesion synthesis (TLS) and can bypass common DNA lesions.

[19] PriS alone preferentially synthesizes strings of DNA; but in combination with PriL, the large subunit, RNA polymerase activity is increased.

[21] AEP enzymes are widespread, and can be found encoded in mobile genetic elements including virus/phages and plasmids.

[14] A great diversity of AEP families has been uncovered in various bacterial plasmids by comparative genomics surveys.

[14] Their evolutionary history is currently unknown, as these found in bacteria and bacteriophages appear too different from their archaeo-eukaryotic homologs for a recent horizontal gene transfer.

A fusion of domains homologous to PriS and PriL, it exhibits both primase and DNA polymerase activity, as well as terminal transferase function.

Asymmetry in the synthesis of leading and lagging strands, with role of DNA primase shown
Steps in DNA synthesis, with role of DNA primase shown
Figure 1. Select multifunctional primases across three domains of life (eukaryota, archaea, and bacteria). The ability of a primase to perform a particular activity is indicated by a check mark. Adapted from. [ 12 ]