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Gene Review

PAPD7  -  PAP associated domain containing 7

Homo sapiens

Synonyms: DNA polymerase sigma, LAK-1, LAK1, Non-canonical poly(A) RNA polymerase PAPD7, PAP-associated domain-containing protein 7, ...
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Disease relevance of POLS

  • Although hepadnavirus replication occurs inside viral nucleocapsids, or cores, biochemical systems for analyzing this reaction are currently limited to unencapsidated Pols expressed in heterologous systems [1].
  • Adenovirus (Ad) DNA polymerase (pol) belongs to the distinct subclass of the polalpha family of DNA pols that employs the precursor terminal protein (pTP) as primer [2].
  • dnaE, the gene encoding one of the two replication-specific DNA polymerases (Pols) of low-GC-content gram-positive bacteria (E. Dervyn et al., Science 294:1716-1719, 2001; R. Inoue et al., Mol. Genet. Genomics 266:564-571, 2001), was cloned from Bacillus subtilis, a model low-GC gram-positive organism [3].
  • Polk reviews prevention of wound infections [4].

High impact information on POLS

  • DNA polymerases (pols) alpha, beta, gamma, delta, and epsilon are the key enzymes required to maintain the integrity of the genome under all these circumstances [5].
  • Here we report that TRF4, an evolutionarily conserved gene necessary for chromosome segregation, encodes a DNA polymerase with beta-polymerase-like properties [6].
  • Interestingly, when filling in a 1 base-pair gap, DNA synthesis and subsequent strand displacement was greatest in the presence of both pols iota and eta [7].
  • Induction of pols eta and zeta occur with T cells, IgM crosslinking, or both stimuli [8].
  • Previously, we have shown that proficient replication through the gamma-HOPdG adduct can be mediated by the sequential action of human DNA polymerases (Pols) iota and kappa, in which Poliota incorporates either pyrimidine opposite gamma-HOPdG, but Polkappa extends only from the cytosine [9].

Biological context of POLS

  • The hTRF4-1 gene maps to chromosome 5p15, a region of frequent copy number alteration in several tumor types [10].
  • The efficiency and fidelity of nucleotide incorporation by high-fidelity replicative DNA polymerases (Pols) are governed by the geometric constraints imposed upon the nascent base pair by the active site [11].
  • Mammalian DNA polymerase kappa (pol kappa), a member of the UmuC/DinB nucleotidyl transferase superfamily, has been implicated in spontaneous mutagenesis [12].
  • In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos [13].
  • Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos). cEPA inhibited the cell growth of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, with LD50 values of 37.5 and 12.5 microM, respectively [13].

Anatomical context of POLS

  • LAK1 is expressed without any structural modification, even on the surface of endothelial cells [14].
  • Moreover, all CD16+ and CD56 (NKH1)+ lymphocytes coexpressed both LAK2 and LAK1 antigens [15].
  • The relative proportions of DNA-polymerases alpha, beta, delta and epsilon (pols alpha, beta, delta and epsilon ) activities in isolated neuronal and astroglial cell fractions from developing, adult and aging rat brain cerebral cortex, were examined [16].
  • Eukaryotic cells contain at least six different Pols, named alpha, beta, gamma, delta, epsilon, and zeta [17].
  • More interestingly, LAK1 is shared by some other cell types, such as monocytes and vascular endothelial cells [18].

Associations of POLS with chemical compounds

  • Translesion synthesis across bulky N2-alkyl guanine DNA adducts by human DNA polymerase kappa [19].
  • Pol epsilon (as well as pols alpha and delta) is optimally active in 100-150 mM potassium glutamate and 15 mM MgCl2 [20].
  • We reported previously that long chain unsaturated fatty acids such as polyunsaturated fatty acids (PUFA) (i.e., eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA)) inhibited the activities of eukaryotic pols in vitro [21].
  • The inhibitory activities against DNA polymerases (pols) of catechin derivatives (i.e., flavan-3-ols) such as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, (+)-catechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-epigallocatechin gallate (EGCg) were investigated [22].
  • In this paper, we present the first detailed biochemical investigation on the mechanism of action of resveratrol towards mammalian pols [23].

Other interactions of POLS


Analytical, diagnostic and therapeutic context of POLS

  • In a case-control study, residents of Galion or Polk Township who had MS were compared to residents who did not have MS [24].
  • Ultrastructural localization of the pols by immuno-electron microscopy revealed pol epsilon to localize predominantly to ring-shaped clusters at electron-dense regions of the nucleus, whereas pol delta was mainly dispersed on fibrous structures [25].


  1. Generation of replication-competent hepatitis B virus nucleocapsids in insect cells. Seifer, M., Hamatake, R., Bifano, M., Standring, D.N. J. Virol. (1998) [Pubmed]
  2. Molecular architecture of adenovirus DNA polymerase and location of the protein primer. Brenkman, A.B., Breure, E.C., van der Vliet, P.C. J. Virol. (2002) [Pubmed]
  3. DNA polymerases of low-GC gram-positive eubacteria: identification of the replication-specific enzyme encoded by dnaE. Barnes, M.H., Miller, S.D., Brown, N.C. J. Bacteriol. (2002) [Pubmed]
  4. Polk reviews prevention of wound infections. Polk, H.C. Hospital infection control. (1978) [Pubmed]
  5. Eukaryotic DNA polymerases. Hubscher, U., Maga, G., Spadari, S. Annu. Rev. Biochem. (2002) [Pubmed]
  6. Pol kappa: A DNA polymerase required for sister chromatid cohesion. Wang, Z., Castaño, I.B., De Las Peñas, A., Adams, C., Christman, M.F. Science (2000) [Pubmed]
  7. 129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation. McDonald, J.P., Frank, E.G., Plosky, B.S., Rogozin, I.B., Masutani, C., Hanaoka, F., Woodgate, R., Gearhart, P.J. J. Exp. Med. (2003) [Pubmed]
  8. Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation. Poltoratsky, V., Woo, C.J., Tippin, B., Martin, A., Goodman, M.F., Scharff, M.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Human DNA polymerase iota promotes replication through a ring-closed minor-groove adduct that adopts a syn conformation in DNA. Wolfle, W.T., Johnson, R.E., Minko, I.G., Lloyd, R.S., Prakash, S., Prakash, L. Mol. Cell. Biol. (2005) [Pubmed]
  10. The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. Walowsky, C., Fitzhugh, D.J., Castaño, I.B., Ju, J.Y., Levin, N.A., Christman, M.F. J. Biol. Chem. (1999) [Pubmed]
  11. Evidence for a Watson-Crick hydrogen bonding requirement in DNA synthesis by human DNA polymerase kappa. Wolfle, W.T., Washington, M.T., Kool, E.T., Spratt, T.E., Helquist, S.A., Prakash, L., Prakash, S. Mol. Cell. Biol. (2005) [Pubmed]
  12. Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene. Ohashi, E., Bebenek, K., Matsuda, T., Feaver, W.J., Gerlach, V.L., Friedberg, E.C., Ohmori, H., Kunkel, T.A. J. Biol. Chem. (2000) [Pubmed]
  13. Mechanism of cell cycle arrest and apoptosis induction by conjugated eicosapentaenoic acid, which is a mammalian DNA polymerase and topoisomerase inhibitor. Yonezawa, Y., Hada, T., Uryu, K., Tsuzuki, T., Nakagawa, K., Miyazawa, T., Yoshida, H., Mizushina, Y. Int. J. Oncol. (2007) [Pubmed]
  14. Biochemical characterization by two-dimensional electrophoresis of lymphocyte antigens involved in cell-to-cell or cell-to-matrix adhesion. Zocchi, M.R., Fabbri, M., Poggi, A., Gianazza, E. Electrophoresis (1991) [Pubmed]
  15. Identification of a new surface molecule expressed by human LGL and LAK cells production of a specific monoclonal antibody and comparison with other NK/LAK markers. Zocchi, M.R., Poggi, A., Mariani, S., Gianazza, E., Rugarli, C. Cell. Immunol. (1989) [Pubmed]
  16. DNA-polymerase alpha, beta, delta and epsilon activities in isolated neuronal and astroglial cell fractions from developing and aging rat cerebral cortex. Raji, N.S., Krishna, T.H., Rao, K.S. Int. J. Dev. Neurosci. (2002) [Pubmed]
  17. DNA polymerase delta, an essential enzyme for DNA transactions. Hindges, R., Hübscher, U. Biol. Chem. (1997) [Pubmed]
  18. LAK1: a novel leucocyte differentiation antigen shared by lymphoid and endothelial cells. Zocchi, M.R., Faravelli, A., Gianazza, E., Pardi, R., Rugarli, C. Basic and applied histochemistry. (1990) [Pubmed]
  19. Translesion synthesis across bulky N2-alkyl guanine DNA adducts by human DNA polymerase kappa. Choi, J.Y., Angel, K.C., Guengerich, F.P. J. Biol. Chem. (2006) [Pubmed]
  20. Further characterization of HeLa DNA polymerase epsilon. Chui, G., Linn, S. J. Biol. Chem. (1995) [Pubmed]
  21. Inhibitory effect of conjugated eicosapentaenoic acid on human DNA topoisomerases I and II. Yonezawa, Y., Tsuzuki, T., Eitsuka, T., Miyazawa, T., Hada, T., Uryu, K., Murakami-Nakai, C., Ikawa, H., Kuriyama, I., Takemura, M., Oshige, M., Yoshida, H., Sakaguchi, K., Mizushina, Y. Arch. Biochem. Biophys. (2005) [Pubmed]
  22. Structural analysis of catechin derivatives as mammalian DNA polymerase inhibitors. Mizushina, Y., Saito, A., Tanaka, A., Nakajima, N., Kuriyama, I., Takemura, M., Takeuchi, T., Sugawara, F., Yoshida, H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  23. Inhibition of mammalian DNA polymerases by resveratrol: mechanism and structural determinants. Locatelli, G.A., Savio, M., Forti, L., Shevelev, I., Ramadan, K., Stivala, L.A., Vannini, V., Hübscher, U., Spadari, S., Maga, G. Biochem. J. (2005) [Pubmed]
  24. Multiple sclerosis in Galion, Ohio: prevalence and results of a case-control study. Hopkins, R.S., Indian, R.W., Pinnow, E., Conomy, J. Neuroepidemiology. (1991) [Pubmed]
  25. Distinctive activities of DNA polymerases during human DNA replication. Rytkönen, A.K., Vaara, M., Nethanel, T., Kaufmann, G., Sormunen, R., Läärä, E., Nasheuer, H.P., Rahmeh, A., Lee, M.Y., Syväoja, J.E., Pospiech, H. FEBS J. (2006) [Pubmed]
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