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2002 Fiscal Year Final Research Report Summary

Study on the testis-specific expression of an error-prone DNA polymerase κ

Research Project

Project/Area Number 13480229
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OHMORI Haruo  Institute for Virus Research Associate Professor, ウイルス研究所, 助教授 (10127061)

Project Period (FY) 2001 – 2002
KeywordsDNA polymerases / DNA damage / mutation / testis / spermatogenesis / infertility / Poly A / promotor
Research Abstract

It has been known that mutations are induced upon DNA damage. Recently, a new type of DNA polymerases (Pols) that are capable of bypassing DNA damaged sites has been identified. These enzymes do not have a proofreading 3'-5' exonuclease activity, and as the result, they are error-prone. For preventing mutations, they should be tightly regulated, so as to exhibit their activities only when needed. We have identified one of such enzymes in mice, Polκ. The Polk gene encoding Polκ is expressed ubiquitously in many tissues, and most strongly in testis. We found that Polk-mRNA transcription is initiated at two different sites. The upstream one is utilized in most tissues, and the downstream one is utilized specifically in testis. Transcription of polk-mRNA in testis seemed to occur at almost equal frequencies from both sites. In testis, two species of Polk-mRNAs are found; testis-specific 3-kb mRNAs are predominant while 5-kb mRNAs commonly found in other tissues are also present, The difference between the two species is not due to the difference in the start site, rather due to the polyadenylation at different sites in the 3'-end. ARE sequence, which is known to render mRNA unstable when present in 3'-untranslated region, is present in the 5-kb mRNA at ten times, but it is absent in the 3-kb mRNAs. Therefore, it seems very likely that 3-kb mRNAs are more stable than the 5-kb mRNA, accumulating in testis.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Ohmori, H.: "The Y-family of DNA polymerases"Molecular Cell. 8. 7 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogi, H: "Expression of human and mouse genes encoding pol kappa: testis-specific developmental regulation and AhR-dependent inducible transcription"Genes to Cells. 6. 943-953 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki, N: "Translesional synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase kappa and Escherichia coli DNA polymerase IV"Biochemistry. 40. 15176-15183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki, N: "Translesion synthesis by human DNA polymerase kappa on a DNA template containing a single stereoisomer of dG-(+)-or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene"Biochemistry. 41. 6100-6106 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogi, T: "Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene PNAS"Proc. Natl. Acad. Sa USA. 99. 15548-15553 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu T: "The absence of DNA polymerase k does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene"Immunology Letters. 86. 265-270 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Ishikawa, N. Uematsu, T. Mizukoshi, S. Iwai, H. Iwasaki, C. Matsutani, F. Hanaoka, R. Ueda, H. Ohmori, T. Todo: "Mutagenic and non-mutagenic bypass of DNA lesions by Drosophila DNA polymerases dpol η and dpol ι"J. Biol. Chem.. 276. 15155-15163 (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] R. L. Levine, H. Miller, A. Grollman, E. Ohashi, H. Ohmori, C. Masutani, F Hanaoka, M. Moriya.: "Translesion DNA synthesis catalyzed by human polη and polκ across 1, N6-ethenodeoxyadenosine"J. Biol. Chem.. 276. 18717-18721 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Ohmori, E. C. Friedberg, R. P. P. Fuchs, M. F. Goodman, F. Hanaoka, D. Hinkle, T. A. Kunkel, C. W. Lawrence, Z. Livneh, T. Nohmi, L. Prakash, S. Prakash, T. Todo, G. C. Walker, Z. Wang, R. Woodgate: "The Y-family of DNA polymerases"Mol. Cell. 8. 7-8 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. O-Wang, K. Kawamura, Y. Tada, H. Ohmori, H. Kimura, S. Sakiyama, M. Tamura.: "DNA polymerase κ, implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer"Cancer Research. 61. 5366-5369 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Ogi, J. Mimura, M. Hikida, H. Fujimoto, Y. Fujii-Kuriyama, H. Ohmori: "Expression of human and mouse genes encoding polκ: testis-specific developmental regulation and AhR-dependent inducible transcription"Genes Cells. 6. 943-953 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] P. M. J. Burgers, E. V. Koonin, L. Blanco, K. C. Burtis, M. F. Christman, W. C. Copeland, E. C. Friedberg, F. Hanaoka, D. C. Hinkle, C. W. Lawrence, M. Nakanishi, H. Ohmori, L. Prakash, S. Prakash, C-A. Reynaud, A. Sugino, T. Todo, Z. Wang, R. Woodgate: "Eukaryotic DNA polymerases: proposed for a revised nomenclature"J. Biol. Chem.. 276. 43487-43490 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Suzuki, E. Ohashi, K. Hayashi, H. Ohmori, A. P. Grollman, S. Shibutani: "Translesion synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase κand Escherichia coli DNA polymerase IV"Biochemistry. 40. 15176-15183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Suzuki, E. Ohashi, A. Kolbanovskiy, N. E. Geacintov, A. P. Grollman, H. Ohmori, S. Shibutani: "Translesion synthesis by human DNA polymerase κ on a DNA template containing a single stereoisomer of dG-(+)- or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti-9,10-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene)"Biochemistry. 41. 6100-6106 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Ogi, Y. Shinkai, K. Tanaka, H. Ohmori: "Polκ protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene"Proc Natl Acad Sci USA.. 99. 15548-15553 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. G. Frank, J. M. Sayer, E. Ohashi, H. Ohmori, D. M. Jerina, R. Woodgate: "Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxadenosine and deoxyguanosine by human DNA polymerase ι"Nucleic Acids Res.. 30. 5284-5292 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I. Y. Yang, H. Miller, Z. Wang, E. G. Frank, H. Ohmori, F. Hanaoka, M. Moriya: "Mammalian translesion DNA synthesis across an acrolein-derived deoxyguanosine adduct. Participation of"J Biol Chem.. 278. 13989-13994 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Shimizu, Y. Shinkai, T. Ogi, H. Ohmori, T. Azuma: "The absence of DNA polymerase κ does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene"Immunol Letters. 86. 265-270 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Vaisman, E. G. Frank, E. Ohashi, S. Iwai, H. Ohmori, F. Hanaoka, R. Woodgate: "Sequence context-dependent translesion replication of cis-syn thymine-thymine dimers by human DNA polymerase ι"DNA Repair. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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