DNA primase small subunit (PRIM1) (PRIM1)

The DNA primase small subunit (PRIM1, also known as p49) is the catalytic component of the eukaryotic DNA primase heterodimer, which functions within the DNA polymerase alpha-primase complex to initiate DNA replication. It synthesizes short RNA primers (typically 9-mers) de novo on single-stranded DNA templates at replication forks, enabling the leading and lagging strand synthesis by providing starting points for DNA polymerases delta and epsilon after initial extension by polymerase alpha. PRIM1 requires a template thymine or cytidine to start priming with an adenine or guanine at the primer's 5'-end, and it incorporates only ribonucleotides despite the presence of deoxyribonucleotides. The subunit partners with the regulatory large subunit (PRIM2 or p58) for stability and activity, undergoing conformational changes via a flexible linker in p58 to switch between initiation and elongation phases. Crystal structures reveal its organization, including an iron-sulfur cluster in the associated complex aiding nucleotide binding. PRIM1 is essential for S-phase progression, recruited via interactions with MCM10 and WDHD1. Biallelic mutations cause rare disorders like primordial dwarfism-immunodeficiency-lipodystrophy syndrome, highlighting its role in growth and immunity. As a drug target, its inhibition disrupts replication but poses challenges due to broad toxicity.

Other names

PRIM1primase DNA polypeptide 1 (49kDa)p49PRI1