DNA polymerase alpha catalytic subunit

Polymerase (DNA directed), alpha 1, catalytic subunit

PDB rendering based on 1k0p.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1K0P, 1K18, 1N5G

Identifiers

Symbols

POLA1 ; NSX; POLA; p180

External IDs

OMIM: 312040 MGI: 99660 HomoloGene: 6802 ChEMBL: 1828 GeneCards: POLA1 Gene

EC number

2.7.7.7

Gene ontology
Molecular function	• nucleotide binding • nucleoside binding • DNA binding • chromatin binding • DNA-directed DNA polymerase activity • DNA primase activity • protein binding • 3'-5' exonuclease activity • metal ion binding • protein heterodimerization activity • 4 iron, 4 sulfur cluster binding
Cellular component	• chromatin • nucleus • nuclear envelope • nucleoplasm • alpha DNA polymerase:primase complex • nucleolus • cytoplasm • nuclear matrix
Biological process	• G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S transition of mitotic cell cycle • mitotic S phase • mitotic cell cycle • telomere maintenance via recombination • telomere maintenance • DNA synthesis involved in DNA repair • DNA replication • DNA replication, synthesis of RNA primer • DNA replication initiation • DNA strand elongation involved in DNA replication • leading strand elongation • lagging strand elongation • DNA repair • nucleotide-excision repair, DNA gap filling • double-strand break repair via nonhomologous end joining • cell proliferation • viral process • translesion synthesis • telomere maintenance via semi-conservative replication • nucleic acid phosphodiester bond hydrolysis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr X:
24.71 – 25.02 Mb

Chr X:
93.3 – 93.63 Mb

PubMed search

DNA polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.^[1]

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.

Interactions

DNA dependent polymerase alpha (Pol α) has been shown to interact with Retinoblastoma protein,^[2] PARP1^[3] and RBMS1.^[4]

References

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

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.

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

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

Both	Movement: Processivity DNA ligase

Termination

Telomere: Telomerase
- TERT
- TERC
- DKC1

Index of genetics

Description	Gene expression DNA replication cycle recombination repair binding proteins Transcription factors regulators nucleic acids RNA RNA binding proteins ribonucleoproteins repeated sequence modification Translation ribosome modification nexins Proteins domains Structure primary secondary tertiary quaternary

Disease	Replication and repair Transcription factor Transcription Translation

DNA polymerase alpha catalytic subunit

Function

Interactions

See also

References

Further reading