• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2003 Fiscal Year Final Research Report Summary

STUDY ON NOVEL REQULATORY MECHANISMA OF DNA REPAIR

Research Project

Project/Area Number 13308041
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

HANAOKA Fumio  OSAKA UNIVERSITY, GRAD. SCH. FRONT. BIOSCI., PROFESSOR, 大学院・生命機能研究科, 教授 (50012670)

Co-Investigator(Kenkyū-buntansha) YOKOI Masayuki  OSAKA UNIVERSITY, GRAD. SCH. FRONT. BIOSCI., RESEACH ASSOCIATE, 大学院・生命機能研究科, 助手 (00322701)
MASUTANI Chikahide  OSAKA UNIVERSITY, GRAD. SCH. FRONT. BIOSCI., RESEACH ASSOCIATE, 大学院・生命機能研究科, 助手 (40241252)
Project Period (FY) 2001 – 2003
Keywordsnucleotide excision repair / translesion synthesis / XPC protein / HR23B protein / xeroderma pigmentosum / thymine DNA glycosylase / DNA polymerase η / DNA polymerase τ
Research Abstract

In order to investigate how DNA repair systems are regulated, we analysed molecular mechanisms of nucleotide excision repair (NER) and translesion synthesis (TLS) in eukaryotic cells, and obtained the following results.
1) The XPC-HR23B protein complex, the initiator of global genome NER, was found to associate with a centrosome protein centrin 2.
2) The XPC-HR23B strongly recognized specific secondary structures of DNA, involving a single-and double-strand junction. A DNase I footprint analysis, using a looped DNA substrate, revealed that a single XPC-HR23B complex protected a distorted site in an asymmetrical manner.
3) While mHR23A KO mice showed no abnormalities, mHR23B KO mice showed impaired embryonic development and a high rate of intrauterine or neonatal death. Surviving animals display a variety of abnormalities, including retarded growth, facial dysmorphology, and male sterility.
4) XPC was found to interact with thymine DNA glycosylase (TDG) in yeast two hybrid screening. By biochemical analyses, XPC interacted with TDG not only physically but also functionally.
5) We identified two fission yeast homologs of budding yeast Rad4 and human XPC, designated Rfp4A and Rhp4B. Rhp4A was found to play roles in GGR and TCR, while Rhp4B acts as an accessory protein in GGR.
6) Human DNA polymerase η (Pol η) catalyzed relatively efficient and accurate TLS past 5R-thymineglycol and 5S-thymineglycol.
7) Both alleles of DNA polymerase τ (Pol τ) gene was found to have null mutation in 129-derived strains of mice. Overall frequency and spectrum of mutation were normal in Pol τ-deficient mice.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Araki, M. et al.: "Centrosome protein centrin/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair"J.Biol.Chem.. 276. 18665-18672 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugasawa, K. et al.: "A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex"DNA Repair. 1. 95-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusumoto, R. et al.: "Translesion synthesis by human DNA polymerase η across thymine glycol lesions"Biochemistry. 41. 6090-6099 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukumoto, Y. et al.: "Two budding yeast RAD4 homologs in fission yeast play different roles in the repair of UV-induced DNA damage"DNA Repair. 1. 833-845 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu, Y. et al.: "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase"EMBO J.. 22. 164-173 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 花岡 文雄: "DNA複製・修復がわかる"羊土社. 133 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Araki, M., Masutani, C., Takemura, M., Uchida, A., Sugasawa, K., Kondoh, J., Ohkuma, Y., Hanaoka, F.: "Centrosome protein centrin 2/caltractin l is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair."J. Biol. Chem.. 276. 18665-18672 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugasawa, K., Shimizu, Y., Iwai, S., Hanaoka, F.: "A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex."DNA Repair. 1. 95-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusumoto, R., Masutani, C., Iwai, S., Hanaoka,F.: "Translesion synthesis by human DNA polymerase η across thymine glycol lesions."Biochemistry. 41. 6090-6099 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukumoto, Y., Hiyama, H., Yokoi, M., Nakaseko, Y., Yanagida, M., Hanaoka,F.: "Two budding yeast RAD4 homologs in fission yeast play different roles in the repair of UV-induced damage."DNA Repair. 1. 833-845 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, Y., Iwai, S., Hanaoka, F., Sugasawa,K.: "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase."EMBO J.. 22. 164-173 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McDonald, J.P., Frank, E.G., Plosky, B.S., Rogozin, I.B., Masutani, C., Hanaoka, F., Woodgate, R., Gearhart,P.J.: "129-derived strains of mice are deficient in DNA polymerase t and have normal immunoglobulin hypermutation."J. Exp. Med.. 198. 635-643 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McCulloch, S.D., Kokoska, R.J., Masutani, C., Iwai, S., Hanaoka, F., Kunkel,T.A.: "Preferential cis-syn thymine dimer bypass by DNA polymerase occurs with biased fidelity."Nature. 428. 97-100 (2004)

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

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi