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Gene Review

POLL  -  polymerase (DNA directed), lambda

Homo sapiens

Synonyms: BETAN, DNA polymerase beta-2, DNA polymerase kappa, DNA polymerase lambda, POLKAPPA, ...
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Disease relevance of POLL

  • Over-expression of human DNA polymerase lambda in E. coli and characterization of the recombinant enzyme [1].
  • We report here that the overexpression of human DNA polymerase kappa, an error-prone enzyme that is up-regulated in lung cancers, induces DNA breaks and stimulates DNA exchanges as well as aneuploidy [2].
  • A shared V beta 13.1 DJ sequence of the CDR3 region, ND beta N, was demonstrated in 49 of 66 V beta 13.1+ clones (74.2%) from the glioma TIL, whereas only 4 of 33 clones (12.1%) were observed in the V beta 13.1+ clones from the PBL (p < 0.001) [3].
  • Further evidence is given of by time rifampicin induction of beta-glucuronidase and beta-N acetylglucosaminidase and its possible relation to hepatitis and pancreatitis [4].

High impact information on POLL

  • These observations have implications for the catalytic mechanism and putative DNA repair functions of Pol lambda [5].
  • Pol lambda makes limited contacts with the template strand at the polymerase active site, and superimposition with Pol beta in a ternary complex suggests a shift in the position of the DNA at the active site that is reminiscent of a deletion intermediate [5].
  • Here, we present a 2.1 A crystal structure of the catalytic core of Pol lambda in complex with DNA containing a two nucleotide gap [5].
  • At low pH, protonation of the beta N terminus and His 147(HC3)beta within these clusters is postulated to destabilize the R-state and promote the acid-triggered, allosteric R-->T switch with concomitant O2 release [6].
  • DNA polymerase lambda, a recently identified X-family homolog of DNA polymerase beta, is hypothesized to be a second polymerase involved in base-excision repair [7].

Biological context of POLL


Anatomical context of POLL


Associations of POLL with chemical compounds

  • This interaction stabilizes the binding of pol lambda to the primer template, thus increasing its affinity for the hydroxyl primer and its processivity in DNA synthesis [13].
  • However, when tested on a template containing a bulky DNA lesion, such as the major cisplatin Pt-d(GpG) adduct, PCNA could not allow translesion synthesis by pol lambda [13].
  • By constructing the truncated Pol lambda, the proline rich region was shown to act in a suppression of its polymerization activity [1].
  • 0. Pol lambda was insensitive to aphidicolin, but was sensitive to dideoxynucleoside triphosphates or N-ethylmaleimide [1].
  • The dRP lyase activity of Pol lambda, in coordination with its polymerization activity, efficiently repaired uracil-containing DNA in an in vitro reconstituted BER reaction [14].

Physical interactions of POLL


Enzymatic interactions of POLL

  • Here we demonstrate that purified pol lambda can efficiently catalyze gap-filling synthesis on DNA substrates mimicking NHEJ [16].
  • Here, we present a kinetic and thermodynamic analysis of the DNA polymerase reaction catalyzed by full length human DNA pol lambda, showing that Mn(2+) favors specifically the catalytic step of nucleotide incorporation [17].

Regulatory relationships of POLL

  • PCNA was found to stimulate efficient synthesis by pol lambda across an abasic (AP) site [13].
  • APE1 has no influence on the strand displacement activity of Pol lambda though it stimulates strand displacement synthesis catalyzed with Pol beta [18].

Other interactions of POLL


Analytical, diagnostic and therapeutic context of POLL

  • In a few cases for which there is a nonconservative substitution in the sequence alignment, a structural comparison shows a positionally and, hence, probably a functionally equivalent residue, e.g., K60 in pol beta and K307 in pol lambda [21].
  • Surface plasmon resonance analysis demonstrated that compound 5 bound selectively to the C-terminal 31kDa domain of pol beta and pol lambda containing a pol beta-like region [22].
  • Immunoprecipitation from extracts of metabolically labeled transformed cells demonstrated that the truncated beta-subunit polypeptide (beta N) was neither transported to the plasma membrane nor assembled into an alpha-beta complex with the endogenous alpha-subunit [23].
  • Cell fractionation experiments showed that the beta N truncated subunit remained unassembled within rough microsomes, suggesting that it never exited from the endoplasmic reticulum (ER) [23].


  1. Over-expression of human DNA polymerase lambda in E. coli and characterization of the recombinant enzyme. Shimazaki, N., Yoshida, K., Kobayashi, T., Toji, S., Tamai, K., Koiwai, O. Genes Cells (2002) [Pubmed]
  2. Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis. Bavoux, C., Leopoldino, A.M., Bergoglio, V., O-Wang, J., Ogi, T., Bieth, A., Judde, J.G., Pena, S.D., Poupon, M.F., Helleday, T., Tagawa, M., Machado, C., Hoffmann, J.S., Cazaux, C. Cancer Res. (2005) [Pubmed]
  3. Shared amino acid sequences in the ND beta N and N alpha regions of the T cell receptors of tumor-infiltrating lymphocytes within malignant glioma. Ebato, M., Nitta, T., Yagita, H., Sato, K., Okumura, K. Eur. J. Immunol. (1994) [Pubmed]
  4. Rifampicin, halothane and glucose as mediators of lysosomal enzyme release and tissue damage. Perry, W. Med. Hypotheses (1988) [Pubmed]
  5. A structural solution for the DNA polymerase lambda-dependent repair of DNA gaps with minimal homology. Garcia-Diaz, M., Bebenek, K., Krahn, J.M., Blanco, L., Kunkel, T.A., Pedersen, L.C. Mol. Cell (2004) [Pubmed]
  6. Structural basis for the root effect in haemoglobin. Mylvaganam, S.E., Bonaventura, C., Bonaventura, J., Getzoff, E.D. Nat. Struct. Biol. (1996) [Pubmed]
  7. Up-regulation of the fidelity of human DNA polymerase lambda by its non-enzymatic proline-rich domain. Fiala, K.A., Duym, W.W., Zhang, J., Suo, Z. J. Biol. Chem. (2006) [Pubmed]
  8. Phosphorylation of human DNA polymerase lambda by the cyclin-dependent kinase Cdk2/cyclin A complex is modulated by its association with proliferating cell nuclear antigen. Frouin, I., Toueille, M., Ferrari, E., Shevelev, I., Hübscher, U. Nucleic Acids Res. (2005) [Pubmed]
  9. Human replication protein A can suppress the intrinsic in vitro mutator phenotype of human DNA polymerase lambda. Maga, G., Shevelev, I., Villani, G., Spadari, S., Hübscher, U. Nucleic Acids Res. (2006) [Pubmed]
  10. DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein A. Maga, G., Ramadan, K., Locatelli, G.A., Shevelev, I., Spadari, S., Hübscher, U. J. Biol. Chem. (2005) [Pubmed]
  11. Identification and characterization of human DNA polymerase beta 2, a DNA polymerase beta -related enzyme. Nagasawa, K., Kitamura, K., Yasui, A., Nimura, Y., Ikeda, K., Hirai, M., Matsukage, A., Nakanishi, M. J. Biol. Chem. (2000) [Pubmed]
  12. DNA polymerase lambda from calf thymus preferentially replicates damaged DNA. Ramadan, K., Shevelev, I.V., Maga, G., Hübscher, U. J. Biol. Chem. (2002) [Pubmed]
  13. Human DNA polymerase lambda functionally and physically interacts with proliferating cell nuclear antigen in normal and translesion DNA synthesis. Maga, G., Villani, G., Ramadan, K., Shevelev, I., Tanguy Le Gac, N., Blanco, L., Blanca, G., Spadari, S., Hübscher, U. J. Biol. Chem. (2002) [Pubmed]
  14. Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair. García-Díaz, M., Bebenek, K., Kunkel, T.A., Blanco, L. J. Biol. Chem. (2001) [Pubmed]
  15. Co-localization in replication foci and interaction of human Y-family members, DNA polymerase pol eta and REVl protein. Tissier, A., Kannouche, P., Reck, M.P., Lehmann, A.R., Fuchs, R.P., Cordonnier, A. DNA Repair (Amst.) (2004) [Pubmed]
  16. DNA polymerase lambda can elongate on DNA substrates mimicking non-homologous end joining and interact with XRCC4-ligase IV complex. Fan, W., Wu, X. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  17. Human DNA polymerase lambda diverged in evolution from DNA polymerase beta toward specific Mn(++) dependence: a kinetic and thermodynamic study. Blanca, G., Shevelev, I., Ramadan, K., Villani, G., Spadari, S., Hübscher, U., Maga, G. Biochemistry (2003) [Pubmed]
  18. Comparison of functional properties of mammalian DNA polymerase lambda and DNA polymerase beta in reactions of DNA synthesis related to DNA repair. Lebedeva, N.A., Rechkunova, N.I., Dezhurov, S.V., Khodyreva, S.N., Favre, A., Blanco, L., Lavrik, O.I. Biochim. Biophys. Acta (2005) [Pubmed]
  19. The human DNA polymerase lambda interacts with PCNA through a domain important for DNA primer binding and the interaction is inhibited by p21/WAF1/CIP1. Maga, G., Blanca, G., Shevelev, I., Frouin, I., Ramadan, K., Spadari, S., Villani, G., Hübscher, U. FASEB J. (2004) [Pubmed]
  20. Single-turnover Kinetic Analysis of the Mutagenic Potential of 8-Oxo-7,8-dihydro-2'-deoxyguanosine during Gap-filling Synthesis Catalyzed by Human DNA Polymerases lambda and beta. Brown, J.A., Duym, W.W., Fowler, J.D., Suo, Z. J. Mol. Biol. (2007) [Pubmed]
  21. Solution structure of the lyase domain of human DNA polymerase lambda. DeRose, E.F., Kirby, T.W., Mueller, G.A., Bebenek, K., Garcia-Diaz, M., Blanco, L., Kunkel, T.A., London, R.E. Biochemistry (2003) [Pubmed]
  22. Cholesterol hemisuccinate: A selective inhibitor of family X DNA polymerases. Ishimaru, C., Kuriyama, I., Shimazaki, N., Koiwai, O., Sakaguchi, K., Kato, I., Yoshida, H., Mizushina, Y. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  23. Expression, localization, and function of an N-terminal half fragment of the rat Na,K-ATPase beta-subunit in HeLa cells. Omori, K., Omori, K., Morimoto, T., Takada, T., Akayama, M., Yoshimori, T., Sabatini, D.D., Tashiro, Y. J. Biochem. (1991) [Pubmed]
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