DNA polymerase eta

Summary

Gene Symbol: DNA polymerase eta
Description: polymerase (DNA directed), eta (RAD 30 related)
Alias: RAD30A, XPV, DNA polymerase eta, DNA-directed DNA polymerase eta, RAD30 homolog A, xeroderma pigmentosum variant type protein homolog
Species: mouse
Products:     DNA polymerase eta

Top Publications

  1. Martomo S, Yang W, Wersto R, Ohkumo T, Kondo Y, Yokoi M, et al. Different mutation signatures in DNA polymerase eta- and MSH6-deficient mice suggest separate roles in antibody diversification. Proc Natl Acad Sci U S A. 2005;102:8656-61 pubmed
    ..T mutations. The data suggest that pol eta preferentially synthesizes a repair patch on the nontranscribed strand, whereas MSH6 functions to generate the patch. ..
  2. Martomo S, Yang W, Vaisman A, Maas A, Yokoi M, Hoeijmakers J, et al. Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase iota. DNA Repair (Amst). 2006;5:392-8 pubmed
    ..Thus, polymerase iota did not contribute to the mutational spectra, even in the absence of polymerase eta...
  3. Faili A, Stary A, Delbos F, Weller S, Aoufouchi S, Sarasin A, et al. A backup role of DNA polymerase kappa in Ig gene hypermutation only takes place in the complete absence of DNA polymerase eta. J Immunol. 2009;182:6353-9 pubmed publisher
    Patients with the variant form of xeroderma pigmentosum (XPV) syndrome have a genetic deficiency in DNA polymerase (Pol) eta, and display accordingly an increased skin sensitivity to UV light, as well as an altered mutation pattern of ..
  4. Martomo S, Saribasak H, Yokoi M, Hanaoka F, Gearhart P. Reevaluation of the role of DNA polymerase theta in somatic hypermutation of immunoglobulin genes. DNA Repair (Amst). 2008;7:1603-8 pubmed publisher
    ..b>DNA polymerase eta has a dominant effect on mutation and may substitute in the absence of polymerase theta to affect the ..
  5. Delbos F, De Smet A, Faili A, Aoufouchi S, Weill J, Reynaud C. Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse. J Exp Med. 2005;201:1191-6 pubmed
    The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase eta, a translesional polymerase whose inactivation is responsible for the xeroderma pigmentosum variant (XP-V) syndrome in humans...
  6. Matsuda T, Bebenek K, Masutani C, Rogozin I, Hanaoka F, Kunkel T. Error rate and specificity of human and murine DNA polymerase eta. J Mol Biol. 2001;312:335-46 pubmed
    We describe here the error specificity of mammalian DNA polymerase eta (pol eta), an enzyme that performs translesion DNA synthesis and may participate in somatic hypermutation of immunoglobulin genes...
  7. Dai G, Wang D, Liu B, Kasik J, Muller H, White R, et al. Three novel paralogs of the rodent prolactin gene family. J Endocrinol. 2000;166:63-75 pubmed
    ..Future experimentation is needed to determine the specific roles of each of these ligands in the biology of pregnancy. ..
  8. Lange S, Tomida J, Boulware K, Bhetawal S, Wood R. The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability. PLoS Genet. 2016;12:e1005759 pubmed publisher
    ..These results validate and encourage the approach of targeting the DNA polymerase activity of pol ζ to sensitize tumors to DNA damaging agents. ..
  9. Kano C, Hanaoka F, Wang J. Analysis of mice deficient in both REV1 catalytic activity and POLH reveals an unexpected role for POLH in the generation of C to G and G to C transversions during Ig gene hypermutation. Int Immunol. 2012;24:169-74 pubmed publisher
    ..These results reveal genetic interactions between REV1 catalytic activity and POLH and identify an alternative pathway, mediated by non-catalytic REV1 and POLH, in the generation of C to G and G to C transversions. ..

More Information

Publications28

  1. Delbos F, Aoufouchi S, Faili A, Weill J, Reynaud C. DNA polymerase eta is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse. J Exp Med. 2007;204:17-23 pubmed
    ..the DNA-binding moiety of the mismatch repair complex constituted by the MSH2-MSH6 proteins, together with DNA polymerase eta (pol eta)...
  2. Dumstorf C, Clark A, Lin Q, Kissling G, Yuan T, Kucherlapati R, et al. Participation of mouse DNA polymerase iota in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer. Proc Natl Acad Sci U S A. 2006;103:18083-8 pubmed
    ..A deficiency in mouse DNA polymerase eta (pol eta) enhanced UV-induced Hprt mutant frequencies...
  3. Ohkumo T, Kondo Y, Yokoi M, Tsukamoto T, Yamada A, Sugimoto T, et al. UV-B radiation induces epithelial tumors in mice lacking DNA polymerase eta and mesenchymal tumors in mice deficient for DNA polymerase iota. Mol Cell Biol. 2006;26:7696-706 pubmed
    b>DNA polymerase eta (Pol eta) is the product of the Polh gene, which is responsible for the group variant of xeroderma pigmentosum, a rare inherited recessive disease which is characterized by susceptibility to sunlight-induced skin cancer...
  4. Hagendoorn J, Tong R, Fukumura D, Lin Q, Lobo J, Padera T, et al. Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis. Cancer Res. 2006;66:3360-4 pubmed
    ..Here, we used a spontaneous carcinogenesis model in the skin of DNA polymerase eta-deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/..
  5. Li S, Zhao Y, Wang J. Analysis of Ig gene hypermutation in Ung(-/-)Polh(-/-) mice suggests that UNG and A:T mutagenesis pathway target different U:G lesions. Mol Immunol. 2013;53:214-7 pubmed publisher
  6. Kanao R, Yokoi M, Ohkumo T, Sakurai Y, Dotsu K, Kura S, et al. UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι. DNA Repair (Amst). 2015;29:139-46 pubmed publisher
  7. Pavlov Y, Rogozin I, Galkin A, Aksenova A, Hanaoka F, Rada C, et al. Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene. Proc Natl Acad Sci U S A. 2002;99:9954-9 pubmed
    To test the hypothesis that inaccurate DNA synthesis by mammalian DNA polymerase eta (pol eta) contributes to somatic hypermutation (SHM) of Ig genes, we measured the error specificity of mouse pol eta during synthesis of each strand of a ..
  8. Ito W, Yokoi M, Sakayoshi N, Sakurai Y, Akagi J, Mitani H, et al. Stalled Pol? at its cognate substrate initiates an alternative translesion synthesis pathway via interaction with REV1. Genes Cells. 2012;17:98-108 pubmed publisher
    ..We propose the model that REV1 and Pol? are involved in DNA damage tolerance via Pol?-REV1 interaction when Pol? fails to bypass its cognate substrates. ..
  9. Busuttil R, Lin Q, Stambrook P, Kucherlapati R, Vijg J. Mutation frequencies and spectra in DNA polymerase eta-deficient mice. Cancer Res. 2008;68:2081-4 pubmed publisher
    ..No differences were found between poleta-null, heterozygous, or littermate control mice. We conclude that the poleta defect is specific for UV damage and has no effect on in vivo mutagenesis in mice. ..
  10. Krijger P, van den Berk P, Wit N, Langerak P, Jansen J, Reynaud C, et al. PCNA ubiquitination-independent activation of polymerase ? during somatic hypermutation and DNA damage tolerance. DNA Repair (Amst). 2011;10:1051-9 pubmed publisher
    ..Taken together, these data support the existence of PCNA ubiquitination-dependent and -independent activation pathways of Pol? during SHM and DNA damage tolerance. ..
  11. Yoon J, Prakash L, Prakash S. Highly error-free role of DNA polymerase eta in the replicative bypass of UV-induced pyrimidine dimers in mouse and human cells. Proc Natl Acad Sci U S A. 2009;106:18219-24 pubmed publisher
    ..These observations have important bearing on how mammalian cells have adapted to avoid the mutagenic and carcinogenic consequences of exposure to sunlight. ..
  12. Guo C, Fischhaber P, Luk Paszyc M, Masuda Y, Zhou J, Kamiya K, et al. Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis. EMBO J. 2003;22:6621-30 pubmed
    ..Our observations suggest that Rev1 plays a role(s) in mediating protein-protein interactions among DNA polymerases required for TLS. The precise function(s) of these interactions during TLS remains to be determined. ..
  13. Masuda K, Ouchida R, Yokoi M, Hanaoka F, Azuma T, Wang J. DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation. Eur J Immunol. 2008;38:2796-805 pubmed publisher
    b>DNA polymerase eta (POLH) is required for the generation of A:T mutations during the somatic hypermutation of Ig genes in germinal center B cells...
  14. Masuda K, Ouchida R, Hikida M, Kurosaki T, Yokoi M, Masutani C, et al. DNA polymerases eta and theta function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes. J Biol Chem. 2007;282:17387-94 pubmed
    ..Mice deficient for DNA polymerase eta (POLH) exhibited an approximately 80% reduction of the mutations at A/T, whereas absence of polymerase (POLQ)..
  15. Saribasak H, Maul R, Cao Z, Yang W, Schenten D, Kracker S, et al. DNA polymerase ? generates tandem mutations in immunoglobulin variable regions. J Exp Med. 2012;209:1075-81 pubmed publisher
    ..Additionally, data on tandem mutations from wild type, Pol?(+/-), Pol?(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol ? may function in the MSH2-MSH6 pathway. ..
  16. Lin Q, Clark A, McCulloch S, Yuan T, Bronson R, Kunkel T, et al. Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice. Cancer Res. 2006;66:87-94 pubmed
    Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer...
  17. Brun J, Mahoney D, Le Boeuf F, Lefebvre C, Sanaei C, Falls T, et al. Oncolytic Vaccinia virus safely and effectively treats skin tumors in mouse models of xeroderma pigmentosum. Int J Cancer. 2013;132:726-31 pubmed publisher
  18. Chen Y, Harris R, Hatahet Z, Chou K. Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities. Proc Natl Acad Sci U S A. 2015;112:E4556-64 pubmed publisher
    ..These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance. ..
  19. Yamada A, Masutani C, Iwai S, Hanaoka F. Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta. Nucleic Acids Res. 2000;28:2473-80 pubmed publisher
    ..XPV encodes DNA polymerase eta, a novel DNA polymerase that belongs to the UmuC/DinB/Rad30 superfamily...