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
External IDs	MGI: 99660 HomoloGene: 6802 GeneCards: POLA1
Gene location (Human) Chr. X chromosome (human)[1] Band Xp22.11-p21.3 Start 24,693,919 bp[1] End 24,996,986 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X C3|X 41.06 cM Start 93,304,767 bp[2] End 93,632,155 bp[2]
RNA expression pattern 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 Cellular component • nuclear envelope • nuclear matrix • nucleolus • chromatin • nucleoplasm • cell 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 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_008892
RefSeq (protein)	NP_001317289 NP_058633	NP_032918
Location (UCSC)	Chr X: 24.69 – 25 Mb	Chr X: 93.3 – 93.63 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

DNA polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.^[5]

Contents

• 
  1 Function
  


• 
  2 Interactions
  


• 
  3 See also
  


• 
  4 References
  


• 
  5 Further reading
  

Function

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.

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. 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 IRF pathway, with consequent overproduction of type I interferons.^[6]

Interactions

DNA dependent polymerase alpha (Pol α) has been shown to interact with Retinoblastoma protein,^[7]PARP1^[8] and RBMS1.^[9]

See also

• DNA Polymerase


• DNA polymerase alpha subunit 2

References

1. 
   ^ ^abc GRCh38: Ensembl release 89: ENSG00000101868 - Ensembl, May 2017
   


2. 
   ^ ^abc GRCm38: Ensembl release 89: ENSMUSG00000006678 - Ensembl, May 2017
   


3. 
   ^ "Human PubMed Reference:"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
   


4. 
   ^ "Mouse PubMed Reference:".
   


5. 
   ^ "Entrez Gene: POLA1 polymerase (DNA directed), alpha 1".
   


6. 
   ^ Starokadomskyy P, Gemelli T, Rios JJ, Xing C, Wang RC, Li H, Pokatayev V, Dozmorov I, Khan S, Miyata N, Fraile G, Raj P, Xu Z, Xu Z, Ma L, Lin Z, Wang H, Yang Y, Ben-Amitai D, Orenstein N, Mussaffi H, Baselga E, Tadini G, Grunebaum E, Sarajlija A, Krzewski K, Wakeland EK, Yan N, de la Morena MT, Zinn AR, Burstein E (2016). "DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis". Nature Immunology. 17 (5): 495–504. doi:10.1038/ni.3409. PMC 4836962. PMID 27019227.
   


7. 
   ^ Takemura M, Kitagawa T, Izuta S, Wasa J, Takai A, Akiyama T, Yoshida S (November 1997). "Phosphorylated retinoblastoma protein stimulates DNA polymerase alpha". Oncogene. 15 (20): 2483–92. doi:10.1038/sj.onc.1201431. PMID 9395244.
   


8. 
   ^ Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Ménissier-de Murcia J (April 1998). "Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication". Nucleic Acids Res. 26 (8): 1891–8. doi:10.1093/nar/26.8.1891. PMC 147507. PMID 9518481.
   


9. 
   ^ Niki T, Galli I, Ariga H, Iguchi-Ariga SM (June 2000). "MSSP, a protein binding to an origin of replication in the c-myc gene, interacts with a catalytic subunit of DNA polymerase alpha and stimulates its polymerase activity". FEBS Lett. 475 (3): 209–12. doi:10.1016/S0014-5793(00)01679-3. PMID 10869558.
   

• 
  Simbulan CM, Suzuki M, Izuta S, Sakurai T, Savoysky E, Kojima K, Miyahara K, Shizuta Y, Yoshida S (Jan 1993). "Poly(ADP-ribose polymerase stimulates DNA polymerase alpha by physical association". J. Biol. Chem. 268 (1): 93–99. PMID 8416979.
  

Further reading

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• 
  Pollok S, Stoepel J, Bauerschmidt C, Kremmer E, Nasheuer HP (2003). "Regulation of eukaryotic DNA replication at the initiation step". Biochem. Soc. Trans. 31 (Pt 1): 266–9. doi:10.1042/BST0310266. PMID 12546699.
  


• 
  Fisher PA, Korn D (1977). "DNA polymerase-alpha. Purification and structural characterization of the near homogeneous enzyme from human KB cells". J. Biol. Chem. 252 (18): 6528–35. PMID 893425.
  


• 
  Dornreiter I, Erdile LF, Gilbert IU, von Winkler D, Kelly TJ, Fanning E (1992). "Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen". EMBO J. 11 (2): 769–76. PMC 556510. PMID 1311258.
  


• 
  Coverley D, Kenny MK, Lane DP, Wood RD (1992). "A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair". Nucleic Acids Res. 20 (15): 3873–80. doi:10.1093/nar/20.15.3873. PMC 334061. PMID 1508673.
  


• 
  Popanda O, Thielmann HW (1992). "The function of DNA polymerases in DNA repair synthesis of ultraviolet-irradiated human fibroblasts". Biochim. Biophys. Acta. 1129 (2): 155–60. doi:10.1016/0167-4781(92)90480-N. PMID 1730053.
  


• 
  Collins KL, Kelly TJ (1991). "Effects of T antigen and replication protein A on the initiation of DNA synthesis by DNA polymerase alpha-primase". Mol. Cell. Biol. 11 (4): 2108–15. PMC 359898. PMID 1848671.
  


• 
  Martelli AM, Cocco L, Manzoli FA (1991). "On the association of DNA polymerase alpha activity with the nuclear matrix in HeLa cells". Cell Biol. Int. Rep. 15 (2): 131–40. doi:10.1016/0309-1651(91)90104-Q. PMID 1903085.
  


• 
  Pearson BE, Nasheuer HP, Wang TS (1991). "Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells". Mol. Cell. Biol. 11 (4): 2081–95. PMC 359896. PMID 2005899.
  


• 
  Matsumoto T, Eki T, Hurwitz J (1991). "Studies on the initiation and elongation reactions in the simian virus 40 DNA replication system". Proc. Natl. Acad. Sci. U.S.A. 87 (24): 9712–6. doi:10.1073/pnas.87.24.9712. PMC 55243. PMID 2175912.
  


• 
  Hsi KL, Copeland WC, Wang TS (1991). "Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus". Nucleic Acids Res. 18 (21): 6231–7. doi:10.1093/nar/18.21.6231. PMC 332486. PMID 2243771.
  


• 
  Wang TS, Pearson BE, Suomalainen HA, Mohandas T, Shapiro LJ, Schröder J, Korn D (1985). "Assignment of the gene for human DNA polymerase alpha to the X chromosome". Proc. Natl. Acad. Sci. U.S.A. 82 (16): 5270–4. doi:10.1073/pnas.82.16.5270. PMC 390549. PMID 2410918.
  


• 
  Knorre DG, Lavrik OI, Nevinsky GA (1988). "Protein-nucleic acid interaction in reactions catalyzed with DNA polymerases". Biochimie. 70 (5): 655–61. doi:10.1016/0300-9084(88)90250-7. PMID 3139084.
  


• 
  Nishida C, Reinhard P, Linn S (1988). "DNA repair synthesis in human fibroblasts requires DNA polymerase delta". J. Biol. Chem. 263 (1): 501–10. PMID 3335506.
  


• 
  Wong SW, Wahl AF, Yuan PM, Arai N, Pearson BE, Arai K, Korn D, Hunkapiller MW, Wang TS (1988). "Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases". EMBO J. 7 (1): 37–47. PMC 454213. PMID 3359994.
  


• 
  Tsuda M, Masuyama M, Katsunuma T (1986). "Inhibition of human DNA polymerase alpha by alpha 1-antichymotrypsin". Cancer Res. 46 (12 Pt 1): 6139–42. PMID 3490907.
  


• 
  Jackson DA, Cook PR (1987). "Different populations of DNA polymerase alpha in HeLa cells". J. Mol. Biol. 192 (1): 77–86. doi:10.1016/0022-2836(86)90465-1. PMID 3820307.
  


• 
  Miller MR, Seighman C, Ulrich RG (1986). "Inhibition of DNA replication and DNA polymerase alpha activity by monoclonal anti-(DNA polymerase alpha) immunoglobulin G and F(ab) fragments". Biochemistry. 24 (25): 7440–5. doi:10.1021/bi00346a061. PMID 4084590.
  


• 
  Bensch KG, Tanaka S, Hu SZ, Wang TS, Korn D (1982). "Intracellular localization of human DNA polymerase alpha with monoclonal antibodies". J. Biol. Chem. 257 (14): 8391–6. PMID 7045121.
  


• 
  Tanaka S, Hu SZ, Wang TS, Korn D (1982). "Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase alpha". J. Biol. Chem. 257 (14): 8386–90. PMID 7085672.
  


• 
  Eckert KA, Kunkel TA (1993). "Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH". Nucleic Acids Res. 21 (22): 5212–20. doi:10.1093/nar/21.22.5212. PMC 310639. PMID 7504813.
  

v t e PDB gallery
1k0p: NMR Structures of the Zinc Finger Domain of Human DNA Polymerase-alpha 1k18: Minimized Average NMR Structure of the Zinc Finger Domain of Human DNA Polymerase-alpha 1n5g: NMR Structures of the Zinc Finger Domain of Human DNA Polymerase-alpha

v t e DNA replication (comparing Prokaryotic to Eukaryotic)
Initiation	Prokaryotic (initiation) Pre-replication complex dnaC Cdc6 Helicase dnaA dnaB T7 Primase dnaG Eukaryotic (preparation in G1 phase) Pre-replication complex Origin recognition complex ORC1 ORC2 ORC3 ORC4 ORC5 ORC6 Cdc6 Cdt1 Minichromosome maintenance MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 Licensing factor Autonomously replicating sequence Single-strand binding protein SSBP2 SSBP3 SSBP4 RNase H RNASEH1 RNASEH2A Helicase: HFM1 Primase: PRIM1 PRIM2 Both Origin of replication/Ori/Replicon Replication fork Lagging and leading strands Okazaki fragments Primer
Replication	Prokaryotic (elongation) DNA polymerase III holoenzyme dnaC dnaE dnaH dnaN dnaQ dnaT dnaX holA holB holC holD holE Replisome DNA ligase DNA clamp Topoisomerase DNA gyrase Prokaryotic DNA polymerase: DNA polymerase I Klenow fragment Eukaryotic (synthesis in S phase) Replication factor C RFC1 Flap endonuclease FEN1 Topoisomerase Replication protein A RPA1 Eukaryotic DNA polymerase: alpha POLA1 POLA2 PRIM1 PRIM2 delta POLD1 POLD2 POLD3 POLD4 epsilon POLE POLE2 POLE3 POLE4 DNA clamp PCNA Control of chromosome duplication Both Movement: Processivity DNA ligase
Termination	Telomere: Telomerase TERT TERC DKC1

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