DNA polymerase alpha

Smith HC, Berezney R (1980) DNA polymerase alpha is tightly bound to the nuclear matrix of actively replicating liver. Biochem Biophys Res Commun 97(4) 1541-1547 Smith HC, Puvion E, Buchholtz LA, Berezney R (1984) Spatial distribution of DNA loop attachment and replicational sites in the nuclear matrix. J Cell Biol 99(5) 1794-1802 Sperry AO, Blasquez VC, Garrard WT (1989) Dysfunction of chromosomal loop attachment sites Illegitimate recombination linked to matrix association regions and topoisomerase 11. Proc Natl Acad Sci USA 86(14) 5497-5501... 

TWn relatively recent developments have added to our knowledge significantly concerning how DNA replication occurs with fidelity or in what molecular biologists and biochemists call a processive polymerase activity. DNA polymerase is the enzyme which actually polymerizes (adds DNA precursors or building blocks) DNA. There are many such DNA polymerases in pro- and eukaryotic cells that have different functions but the main enzyme in prokaryotes is DNA polymerase 111 and in Eukaryotes. DNA polymerases alpha, delta, and epsilon. All four of these DNA polymerases are made of subunits. 

Mizushina Y, Ishidoh T, Kamisuki S, Nakazawa S, Takemura M, Sugawara F, Yoshida H, Sakaguchi K. 2003. Flavonoid glycoside A new inhibitor of eukaryotic DNA polymerase alpha and a new carrier for inhibitor-affinity chromatography. Biochem Biophys Res Com 301 480-487. 

C. H. Lee, M. Liu, K. L. Sie, and M. S. Lee, Prostate-specific antigen promoter driven gene therapy targeting DNA polymerase-alpha and topoisomerase II alpha in prostate cancer, Anticancer Res. 16 1805 (1996). 

Sylvia, V, Curtin, G., Norman, J., Stec, J., and Busbee, D., 1988, Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate. Cell 54 651-658. 

DNA polymerase alpha was up-regulated following low-level sarin exposure. Since mammalian DNA replication (and possibly DNA repair) mechanisms utilize DNA... 

Walter J, Newport J. Initiation of eukaryotic DNA replication origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha. Mol. Cell 2000 5 617-627. Zou L, Stillman B. Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled... 

De Falco M, Ferrari E, De Felice M, Rossi M, Flubscher U, 82. Pisani FM. The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase. EMBO Rep. 2007 8 99-103. 

Coates, P. J., Hales, S. A., and Hall, P. A. (1996) The association between cell proliferation and apoptosis studies using the cell cycle associated proteins Ki-67 and DNA polymerase alpha. J. Pathol. 178, 71-77. 

Williams MV, Winters T, Waddel KS. 1987. In vivo effects of mercury (II) on deoxyuridine triphosphate nucleotidohydrolase, DNA polymerase (alpha, beta), and uracil-DNA glycosylase activities in cultured human cells Relationship to DNA damage, DNA repair, and cytotoxicity. Mol Pharmacol 31 200-207. 

Kaiserman HB, Benbow RM (1987) Characterization of a stable major DNA polymerase alpha species devoid of DNA primase activity. Nucleic Acids Res 15 10249-10265 Kaufman BT (1974) Methotrexate-agarose in the purification of dihydrofolate reductase. Methods... 

Fludarabine is a purine antimetabolite. Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidara-bine. Fludarabine s metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thus inhibiting DNA synthesis. It is indicated in refactory or progressive chronic B-ceU lymphocytic leukemia. 

D Urso, G., Grallert, B., and Nurse, P. (1995). DNA polymerase alpha, a component of the replication initiation complex, is essential for the checkpoint coupling S phase to mitosis in fission yeast, y Cell Sci. I08(Pt 9), 3109—3118. 

Dantzer F, Nasheuer HP, Vonesch JL et al. Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-ptimasc complex A link between DNA strand break detection and DNA replication. Nucleic Adds Res 1998 26(8) 1891-1898. 

Richardson, R, Kuchta, R., Mazurkiewicz, A., Richardson, K. (2000). Polymerization of 2 -fluoro- and 2 -0-methyl-dNTPs by human DNA polymerase alpha, polymerase gamma, and pri-mase. Biochem Pharmacol, 59 (9), 1045-1052. 

E. (1989) An unusual polyanion from Physarum polycephalum that inhibits homologous DNA polymerase alpha in vitro. Biochemistry, 28, 5219-5226. 

Wawra, E., 2 11ner, H., Schaur, R.J., Tillian, H.M. and Schauenstein, E. (1986) The inhibitory effect of 4-hydroxy-nonenal on DNA-polymerase alpha and beta from rat liver and rapidly dividing Yoshida ascites hepatoma. Cell Biochem. Fund. 4, 31-36. 

Birkus G, Rejman D, Otmar M, Votruba I, Rosenberg I, Holy A (2004) The substrate activity of (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine diphosphate toward DNA polymerases alpha, delta and epsilon. Antivir Chem Chemother 15 23-33 Magee WC, Valiaeva N, Beadle JR, Richman DD, Hostetler KY, Evans DH (2011) Antimicrob Agents Chemother 55(ll) 5063-5072... 

Maeda N, Kokai Y, Ohtani S, Sahara H, Kuriyama I, Kamisuki S, Takahashi S, Sakaguehi K, Sugawara F, Yoshida H, Sato N, Mizushina Y (2007) Anti-tumor effects of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha. Biochem Biophys Res Commun 352(2) 390-396... 

N.N. Khan, G.E. Wright, L.W. Dudycz, and N.C. Brown, Butylphenyl dGTP a selective and potent inhibitor of mammalian DNA polymerase alpha. Nucleic Acid Res. 12 3695 (1984). 

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