Polymerase (DNA directed), alpha 1

Polymerase (DNA directed), alpha 1, catalytic subunit

PDB rendering based on 1k0p.

Available structures
PDB	1K0P, 1K18, 1N5G

Identifiers

Symbols

POLA1; DKFZp686K1672; POLA; p180

External IDs

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

EC number

2.7.7.7

Gene Ontology
Molecular function	• nucleotide binding • nucleoside binding • DNA binding • DNA binding • chromatin binding • double-stranded DNA binding • DNA-directed DNA polymerase activity • DNA-directed DNA polymerase activity • DNA primase activity • protein binding • transferase activity • nucleotidyltransferase activity • purine nucleotide binding • pyrimidine nucleotide binding • metal ion binding • protein heterodimerization activity
Cellular component	• chromatin • nucleus • nuclear envelope • nucleoplasm • nucleoplasm • nucleoplasm • alpha DNA polymerase:primase complex • alpha DNA polymerase:primase complex • nucleolus • nucleolus • cytoplasm • nuclear matrix • intracellular membrane-bounded organelle
Biological process	• DNA replication checkpoint • G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S phase of mitotic cell cycle • S phase of mitotic cell cycle • S phase of mitotic cell cycle • M/G1 transition of mitotic cell cycle • mitotic cell cycle • telomere maintenance via recombination • telomere maintenance • DNA synthesis involved in DNA repair • nucleobase, nucleoside, nucleotide and nucleic acid metabolic process • DNA replication • DNA replication, synthesis of RNA primer • DNA-dependent DNA replication initiation • DNA-dependent DNA replication initiation • DNA strand elongation involved in DNA replication • DNA strand elongation involved in DNA replication • leading strand elongation • lagging strand elongation • DNA repair • double-strand break repair via nonhomologous end joining • cell proliferation • telomere maintenance via semi-conservative replication • interspecies interaction between organisms
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:
90.55 – 90.88 Mb

PubMed search

[1]

[2]

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

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 and during lagging-strand synthesis of Okazaki fragments.

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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5422.
^ Takemura, M; Kitagawa T, Izuta S, Wasa J, Takai A, Akiyama T, Yoshida S (Nov. 1997). "Phosphorylated retinoblastoma protein stimulates DNA polymerase alpha". Oncogene (ENGLAND) 15 (20): 2483–92. doi:10.1038/sj.onc.1201431. ISSN 0950-9232. PMID 9395244.
^ Dantzer, F; Nasheuer H P, Vonesch J L, de Murcia G, Ménissier-de Murcia J (Apr. 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. (ENGLAND) 26 (8): 1891–8. doi:10.1093/nar/26.8.1891. ISSN 0305-1048. PMC 147507. PMID 9518481. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147507.
^ Niki, T; Galli I, Ariga H, Iguchi-Ariga S M (Jun. 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. (NETHERLANDS) 475 (3): 209–12. doi:10.1016/S0014-5793(00)01679-3. ISSN 0014-5793. PMID 10869558.

Pollok S, Stoepel J, Bauerschmidt C, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=556510.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=334061.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359898.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359896.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=55243.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332486.
Wang TS, Pearson BE, Suomalainen HA, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=390549.
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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=454213.
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, et al. (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 (1994). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310639.

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

Polymerase (DNA directed), alpha 1

Interactions

References

Further reading