DNA polymerase alpha catalytic subunit: Difference between revisions

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== Further reading ==
== Further reading ==
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{{refbegin | 2}}
*{{cite journal |vauthors=Pollok S, Stoepel J, Bauerschmidt C, Kremmer E, Nasheuer HP | title = Regulation of eukaryotic DNA replication at the initiation step. | journal = Biochem. Soc. Trans. | volume = 31 | issue = Pt 1 | pages = 266–9 | year = 2003 | pmid = 12546699 | doi = 10.1042/BST0310266 }}
*{{cite journal |vauthors=Pollok S, Stoepel J, Bauerschmidt C, Kremmer E, Nasheuer HP | title = Regulation of eukaryotic DNA replication at the initiation step | journal = Biochem. Soc. Trans. | volume = 31 | issue = Pt 1 | pages = 266–9 | year = 2003 | pmid = 12546699 | doi = 10.1042/BST0310266 }}
*{{cite journal |vauthors=Fisher PA, Korn D | title = DNA polymerase-alpha. Purification and structural characterization of the near homogeneous enzyme from human KB cells. | journal = J. Biol. Chem. | volume = 252 | issue = 18 | pages = 6528–35 | year = 1977 | pmid = 893425 | doi =  }}
*{{cite journal |vauthors=Fisher PA, Korn D | title = DNA polymerase-alpha. Purification and structural characterization of the near homogeneous enzyme from human KB cells | journal = J. Biol. Chem. | volume = 252 | issue = 18 | pages = 6528–35 | year = 1977 | pmid = 893425 | doi =  }}
*{{cite journal |vauthors=Dornreiter I, Erdile LF, Gilbert IU, von Winkler D, Kelly TJ, Fanning E | title = Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen. | journal = EMBO J. | volume = 11 | issue = 2 | pages = 769–76 | year = 1992 | pmid = 1311258 | pmc = 556510 | doi =  }}
*{{cite journal |vauthors=Dornreiter I, Erdile LF, Gilbert IU, von Winkler D, Kelly TJ, Fanning E | title = Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen | journal = EMBO J. | volume = 11 | issue = 2 | pages = 769–76 | year = 1992 | pmid = 1311258 | pmc = 556510 | doi =  }}
*{{cite journal |vauthors=Coverley D, Kenny MK, Lane DP, Wood RD | title = A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair. | journal = Nucleic Acids Res. | volume = 20 | issue = 15 | pages = 3873–80 | year = 1992 | pmid = 1508673 | pmc = 334061 | doi = 10.1093/nar/20.15.3873 }}
*{{cite journal |vauthors=Coverley D, Kenny MK, Lane DP, Wood RD | title = A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair | journal = Nucleic Acids Res. | volume = 20 | issue = 15 | pages = 3873–80 | year = 1992 | pmid = 1508673 | pmc = 334061 | doi = 10.1093/nar/20.15.3873 }}
*{{cite journal |vauthors=Popanda O, Thielmann HW | title = The function of DNA polymerases in DNA repair synthesis of ultraviolet-irradiated human fibroblasts. | journal = Biochim. Biophys. Acta | volume = 1129 | issue = 2 | pages = 155–60 | year = 1992 | pmid = 1730053 | doi = 10.1016/0167-4781(92)90480-N }}
*{{cite journal |vauthors=Popanda O, Thielmann HW | title = The function of DNA polymerases in DNA repair synthesis of ultraviolet-irradiated human fibroblasts | journal = Biochim. Biophys. Acta | volume = 1129 | issue = 2 | pages = 155–60 | year = 1992 | pmid = 1730053 | doi = 10.1016/0167-4781(92)90480-N }}
*{{cite journal |vauthors=Collins KL, Kelly TJ | title = Effects of T antigen and replication protein A on the initiation of DNA synthesis by DNA polymerase alpha-primase. | journal = Mol. Cell. Biol. | volume = 11 | issue = 4 | pages = 2108–15 | year = 1991 | pmid = 1848671 | pmc = 359898 | doi =  }}
*{{cite journal |vauthors=Collins KL, Kelly TJ | title = Effects of T antigen and replication protein A on the initiation of DNA synthesis by DNA polymerase alpha-primase | journal = Mol. Cell. Biol. | volume = 11 | issue = 4 | pages = 2108–15 | year = 1991 | pmid = 1848671 | pmc = 359898 | doi =  }}
*{{cite journal |vauthors=Martelli AM, Cocco L, Manzoli FA | title = On the association of DNA polymerase alpha activity with the nuclear matrix in HeLa cells. | journal = Cell Biol. Int. Rep. | volume = 15 | issue = 2 | pages = 131–40 | year = 1991 | pmid = 1903085 | doi = 10.1016/0309-1651(91)90104-Q }}
*{{cite journal |vauthors=Martelli AM, Cocco L, Manzoli FA | title = On the association of DNA polymerase alpha activity with the nuclear matrix in HeLa cells | journal = Cell Biol. Int. Rep. | volume = 15 | issue = 2 | pages = 131–40 | year = 1991 | pmid = 1903085 | doi = 10.1016/0309-1651(91)90104-Q }}
*{{cite journal |vauthors=Pearson BE, Nasheuer HP, Wang TS | title = Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. | journal = Mol. Cell. Biol. | volume = 11 | issue = 4 | pages = 2081–95 | year = 1991 | pmid = 2005899 | pmc = 359896 | doi =  }}
*{{cite journal |vauthors=Pearson BE, Nasheuer HP, Wang TS | title = Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells | journal = Mol. Cell. Biol. | volume = 11 | issue = 4 | pages = 2081–95 | year = 1991 | pmid = 2005899 | pmc = 359896 | doi =  }}
*{{cite journal |vauthors=Matsumoto T, Eki T, Hurwitz J | title = Studies on the initiation and elongation reactions in the simian virus 40 DNA replication system. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 24 | pages = 9712–6 | year = 1991 | pmid = 2175912 | pmc = 55243 | doi = 10.1073/pnas.87.24.9712 }}
*{{cite journal |vauthors=Matsumoto T, Eki T, Hurwitz J | title = Studies on the initiation and elongation reactions in the simian virus 40 DNA replication system | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 24 | pages = 9712–6 | year = 1991 | pmid = 2175912 | pmc = 55243 | doi = 10.1073/pnas.87.24.9712 }}
*{{cite journal |vauthors=Hsi KL, Copeland WC, Wang TS | title = Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus. | journal = Nucleic Acids Res. | volume = 18 | issue = 21 | pages = 6231–7 | year = 1991 | pmid = 2243771 | pmc = 332486 | doi = 10.1093/nar/18.21.6231 }}
*{{cite journal |vauthors=Hsi KL, Copeland WC, Wang TS | title = Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus | journal = Nucleic Acids Res. | volume = 18 | issue = 21 | pages = 6231–7 | year = 1991 | pmid = 2243771 | pmc = 332486 | doi = 10.1093/nar/18.21.6231 }}
*{{cite journal |vauthors=Wang TS, Pearson BE, Suomalainen HA, Mohandas T, Shapiro LJ, Schröder J, Korn D | title = Assignment of the gene for human DNA polymerase alpha to the X chromosome. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 82 | issue = 16 | pages = 5270–4 | year = 1985 | pmid = 2410918 | pmc = 390549 | doi = 10.1073/pnas.82.16.5270 }}
*{{cite journal |vauthors=Wang TS, Pearson BE, Suomalainen HA, Mohandas T, Shapiro LJ, Schröder J, Korn D | title = Assignment of the gene for human DNA polymerase alpha to the X chromosome | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 82 | issue = 16 | pages = 5270–4 | year = 1985 | pmid = 2410918 | pmc = 390549 | doi = 10.1073/pnas.82.16.5270 }}
*{{cite journal |vauthors=Knorre DG, Lavrik OI, Nevinsky GA | title = Protein-nucleic acid interaction in reactions catalyzed with DNA polymerases. | journal = Biochimie | volume = 70 | issue = 5 | pages = 655–61 | year = 1988 | pmid = 3139084 | doi = 10.1016/0300-9084(88)90250-7 }}
*{{cite journal |vauthors=Knorre DG, Lavrik OI, Nevinsky GA | title = Protein-nucleic acid interaction in reactions catalyzed with DNA polymerases | journal = Biochimie | volume = 70 | issue = 5 | pages = 655–61 | year = 1988 | pmid = 3139084 | doi = 10.1016/0300-9084(88)90250-7 }}
*{{cite journal |vauthors=Nishida C, Reinhard P, Linn S | title = DNA repair synthesis in human fibroblasts requires DNA polymerase delta. | journal = J. Biol. Chem. | volume = 263 | issue = 1 | pages = 501–10 | year = 1988 | pmid = 3335506 | doi =  }}
*{{cite journal |vauthors=Nishida C, Reinhard P, Linn S | title = DNA repair synthesis in human fibroblasts requires DNA polymerase delta | journal = J. Biol. Chem. | volume = 263 | issue = 1 | pages = 501–10 | year = 1988 | pmid = 3335506 | doi =  }}
*{{cite journal |vauthors=Wong SW, Wahl AF, Yuan PM, Arai N, Pearson BE, Arai K, Korn D, Hunkapiller MW, Wang TS | title = Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. | journal = EMBO J. | volume = 7 | issue = 1 | pages = 37–47 | year = 1988 | pmid = 3359994 | pmc = 454213 | doi =  }}
*{{cite journal |vauthors=Wong SW, Wahl AF, Yuan PM, Arai N, Pearson BE, Arai K, Korn D, Hunkapiller MW, Wang TS | title = Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases | journal = EMBO J. | volume = 7 | issue = 1 | pages = 37–47 | year = 1988 | pmid = 3359994 | pmc = 454213 | doi =  }}
*{{cite journal |vauthors=Tsuda M, Masuyama M, Katsunuma T | title = Inhibition of human DNA polymerase alpha by alpha 1-antichymotrypsin. | journal = Cancer Res. | volume = 46 | issue = 12 Pt 1 | pages = 6139–42 | year = 1986 | pmid = 3490907 | doi =  }}
*{{cite journal |vauthors=Tsuda M, Masuyama M, Katsunuma T | title = Inhibition of human DNA polymerase alpha by alpha 1-antichymotrypsin | journal = Cancer Res. | volume = 46 | issue = 12 Pt 1 | pages = 6139–42 | year = 1986 | pmid = 3490907 | doi =  }}
*{{cite journal |vauthors=Jackson DA, Cook PR | title = Different populations of DNA polymerase alpha in HeLa cells. | journal = J. Mol. Biol. | volume = 192 | issue = 1 | pages = 77–86 | year = 1987 | pmid = 3820307 | doi = 10.1016/0022-2836(86)90465-1 }}
*{{cite journal |vauthors=Jackson DA, Cook PR | title = Different populations of DNA polymerase alpha in HeLa cells | journal = J. Mol. Biol. | volume = 192 | issue = 1 | pages = 77–86 | year = 1987 | pmid = 3820307 | doi = 10.1016/0022-2836(86)90465-1 }}
*{{cite journal |vauthors=Miller MR, Seighman C, Ulrich RG | title = Inhibition of DNA replication and DNA polymerase alpha activity by monoclonal anti-(DNA polymerase alpha) immunoglobulin G and F(ab) fragments. | journal = Biochemistry | volume = 24 | issue = 25 | pages = 7440–5 | year = 1986 | pmid = 4084590 | doi = 10.1021/bi00346a061 }}
*{{cite journal |vauthors=Miller MR, Seighman C, Ulrich RG | title = Inhibition of DNA replication and DNA polymerase alpha activity by monoclonal anti-(DNA polymerase alpha) immunoglobulin G and F(ab) fragments | journal = Biochemistry | volume = 24 | issue = 25 | pages = 7440–5 | year = 1986 | pmid = 4084590 | doi = 10.1021/bi00346a061 }}
*{{cite journal |vauthors=Bensch KG, Tanaka S, Hu SZ, Wang TS, Korn D | title = Intracellular localization of human DNA polymerase alpha with monoclonal antibodies. | journal = J. Biol. Chem. | volume = 257 | issue = 14 | pages = 8391–6 | year = 1982 | pmid = 7045121 | doi =  }}
*{{cite journal |vauthors=Bensch KG, Tanaka S, Hu SZ, Wang TS, Korn D | title = Intracellular localization of human DNA polymerase alpha with monoclonal antibodies | journal = J. Biol. Chem. | volume = 257 | issue = 14 | pages = 8391–6 | year = 1982 | pmid = 7045121 | doi =  }}
*{{cite journal |vauthors=Tanaka S, Hu SZ, Wang TS, Korn D | title = Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase alpha. | journal = J. Biol. Chem. | volume = 257 | issue = 14 | pages = 8386–90 | year = 1982 | pmid = 7085672 | doi =  }}
*{{cite journal |vauthors=Tanaka S, Hu SZ, Wang TS, Korn D | title = Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase alpha | journal = J. Biol. Chem. | volume = 257 | issue = 14 | pages = 8386–90 | year = 1982 | pmid = 7085672 | doi =  }}
*{{cite journal |vauthors=Eckert KA, Kunkel TA | title = Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH. | journal = Nucleic Acids Res. | volume = 21 | issue = 22 | pages = 5212–20 | year = 1993 | pmid = 7504813 | pmc = 310639 | doi = 10.1093/nar/21.22.5212 }}
*{{cite journal |vauthors=Eckert KA, Kunkel TA | title = Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH | journal = Nucleic Acids Res. | volume = 21 | issue = 22 | pages = 5212–20 | year = 1993 | pmid = 7504813 | pmc = 310639 | doi = 10.1093/nar/21.22.5212 }}
{{refend}}
{{refend}}


Latest revision as of 22:32, 5 September 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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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.

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.[2]

Interactions

DNA dependent polymerase alpha (Pol α) has been shown to interact with Retinoblastoma protein,[3] PARP1[4] and RBMS1.[5]

See also

References

  1. ↑ "Entrez Gene: POLA1 polymerase (DNA directed), alpha 1".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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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