DNA primase small subunit
Also known as: PRIM1
Function
Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex - primosome/replisome) which play an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit. Synthesizes 9-mer RNA primers (also known as the 'unit length' RNA primers). Incorporates only ribonucleotides in the presence of ribo- and deoxy-nucleotide triphosphates (rNTPs, dNTPs). Requires template thymine or cytidine to start the RNA primer synthesis, with an adenine or guanine at its 5'-end. Binds single stranded DNA (By similarity).
Classification
- Family (Pfam)
- PF01896 DNA_primase_S
- InterPro
- DNA_primase_S, DNA_primase_ssu_euk/arc
- Functional cluster
- Nucleotide & Amino-Acid Biosynthesis Enzymes
Experimental structures · PDB · 23
- 4BPU X-ray 2.70A
- 4BPW X-ray 3.00A
- 4BPX X-ray 3.40A
- 4LIK X-ray 1.70A
- 4LIL X-ray 2.60A
- 4MHQ X-ray 2.20A
- 4RR2 X-ray 2.65A
- 5EXR X-ray 3.60A
- 6R4S X-ray 2.75A
- 6R4T X-ray 2.35A
- 6R4U X-ray 2.20A
- 6R5D X-ray 1.95A
- … and 11 more
A predicted model is available from AlphaFold.
Gene Ontology · 9
- GO:0005658 alpha DNA polymerase:primase complex
- GO:0016020 membrane
- GO:0005654 nucleoplasm
- GO:0003899 DNA-directed RNA polymerase activity
- GO:0000287 magnesium ion binding
- GO:0032553 ribonucleotide binding
- GO:0008270 zinc ion binding
- GO:0006270 DNA replication initiation
- GO:0006269 DNA replication, synthesis of primer
Disease associations
Drugs targeting this protein · 6
- FLUDARABINE PHOSPHATE inhibitor
- GEMCITABINE HYDROCHLORIDE inhibitor
- CLOFARABINE inhibitor
- TROXACITABINE inhibitor
- ASPACYTARABINE inhibitor
- CYTARABINE inhibitor
Related proteins · sequence + function similarity
- DNA primase small subunit 0.97
- DNA primase small subunit 0.88
- DNA primase small subunit 0.88
- DNA primase small subunit 0.87
- DNA primase small subunit 0.87
- DNA primase small subunit 0.84
- DNA primase small subunit 0.84
- DNA primase small subunit PriS 0.52
- DNA primase small subunit PriS 0.47
- DNA primase small subunit PriS 0.47
- DNA primase small subunit PriS 0.47
- DNA-directed primase/polymerase protein 0.46
Co-cited proteins · studied together in the literature
- DNA primase large subunit 6 shared papers
- DNA polymerase alpha subunit B 2 shared papers
- DNA polymerase alpha catalytic subunit 2 shared papers
- DNA primase large subunit 1 shared papers
- DNA primase small subunit 1 shared papers
- DNA polymerase alpha catalytic subunit 1 shared papers
Literature · 14 cited papers
- PRIM1 deficiency causes a distinctive primordial dwarfism syndrome. Genes Dev. · 2020
- Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine. ACS Chem. Biol. · 2019
- Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome. J. Biol. Chem. · 2016
- Crystal structure of the human primase. J. Biol. Chem. · 2015
- Insights into eukaryotic primer synthesis from structures of the p48 subunit of human DNA primase. J. Mol. Biol. · 2014
- Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering. Proc. Natl. Acad. Sci. U.S.A. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase. J. Biol. Chem. · 2007
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Primase activity of human DNA polymerase alpha-primase. Divalent cations stabilize the enzyme activity of the p48 subunit. J. Biol. Chem. · 1998
- … and 2 more in the literature graph