DNA polymerase alpha catalytic subunit

POLA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1K0P, 1K18, 1N5G, 4Q5V, 4QCL, 4Y97, 5EXR, 5IUD
Identifiers
Aliases	POLA1, NSX, POLA, p180, Polymerase (DNA directed), alpha 1, polymerase (DNA) alpha 1, catalytic subunit, DNA polymerase alpha 1, catalytic subunit, VEODS
External IDs	OMIM: 312040; MGI: 99660; HomoloGene: 6802; GeneCards: POLA1; OMA:POLA1 - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xp22.11-p21.3 Start 24,693,873 bp[1] End 24,996,986 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X C3|X 41.06 cM Start 92,348,373 bp[2] End 92,675,761 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve Achilles tendon oocyte ganglionic eminence secondary oocyte bone marrow cells corpus callosum gastrocnemius muscle thymus popliteal artery Top expressed in morula ureter blastocyst abdominal wall dermis secondary oocyte vas deferens Paneth cell hand maxillary prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity 4 iron, 4 sulfur cluster binding nucleotidyltransferase activity nucleoside binding iron-sulfur cluster binding chromatin binding metal ion binding protein binding nucleic acid binding protein kinase binding DNA-directed DNA polymerase activity nucleotide binding DNA binding DNA replication origin binding purine nucleotide binding protein heterodimerization activity single-stranded DNA binding pyrimidine nucleotide binding Cellular component nuclear envelope nuclear matrix nucleolus chromatin nucleoplasm nucleus cytoplasm cytosol alpha DNA polymerase:primase complex Biological process DNA synthesis involved in DNA repair lagging strand elongation regulation of transcription involved in G1/S transition of mitotic cell cycle DNA replication leading strand elongation cell population proliferation viral process double-strand break repair via nonhomologous end joining DNA strand elongation involved in DNA replication DNA replication, synthesis of RNA primer telomere maintenance via semi-conservative replication G1/S transition of mitotic cell cycle DNA replication initiation DNA repair nucleotide-excision repair DNA synthesis involved in UV-damage excision repair mitotic DNA replication initiation synthesis of RNA primer involved in mitotic DNA replication Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5422 18968 Ensembl ENSG00000101868 ENSMUSG00000006678 UniProt P09884 P33609 RefSeq (mRNA) NM_016937 NM_001330360 NM_001378303 NM_008892 RefSeq (protein) NP_001317289 NP_058633 NP_001365232 NP_032918 Location (UCSC) Chr X: 24.69 – 25 Mb Chr X: 92.35 – 92.68 Mb PubMed search [3] [4]
Wikidata
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DNA polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.^[5]

Function

This gene encodes the p180 catalytic subunit of DNA polymerase α-primase. Pol α has limited processivity and lacks 3′ exonuclease activity for proofreading errors. Thus it is not well suited to efficiently and accurately copy long templates (unlike Pol Delta and Epsilon). Instead it plays a more limited role in replication. Pol α is responsible for the initiation of DNA replication at origins of replication (on both the leading and lagging strands) and during synthesis of Okazaki fragments on the lagging strand. The Pol α complex (pol α-DNA primase complex) consists of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1 and PRIM2 respectively. Once primase has created the RNA primer, Pol α starts replication elongating the primer with ~20 nucleotides.

Clinical significance

In addition to its role during DNA replication, POLA1 plays a role in type I interferon activation. The POLA1 gene was found to be the site of a mutation resulting in X-linked reticulate pigmentary disorder (XLPDR), OMIM 301220). This leads to altered mRNA splicing and decreased expression of POLA1 protein to a level that does not impair DNA replication. The reduction in POLA1 expression is accompanied by marked reduction in cytosolic RNA:DNA hybrid molecules and a concomitant hyperactivation of the IRF3 pathway, with consequent overproduction of type I interferons.^[7]

Moreover, POLA1 deficiency, typical for XLPDR, also impair direct cytotoxicity of NK cells. POLA1 inhibition or a natural deficiency (XLPDR) affects the way the lytic granules secreted toward target cells. As a result, NK cells in XLPDR patients display functional deficiency. Interestingly, the POLA1 deficiency typical for XLPDR is not associated with any genomic damages or cell cycle arrest.^[8][9]

While the XLPDR mutation is resided in intron 13th, other somatic mutations in POLA1 were also described. Somatic mutation are associated with more profound deficiency of POLA1, with develops into X-linked intellectual disability (XLID). In a case of non-XLPDR mutations, beside of type I interferon signature patients also display mild to medium signs of intellectual disability, cell cycle arrest, proportionate short stature, microcephaly and hypogonadism.^[10]

Interactions

DNA dependent polymerase alpha (Pol α) has been shown to interact with MCM4 and GINS1,^[8] Retinoblastoma protein,^[11] PARP1^[12][13] and RBMS1.^[14]

See also

• DNA Polymerase
• DNA polymerase alpha subunit 2

References

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human DNA polymerase alpha catalytic subunit

Further reading

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