2002 Fiscal Year Final Research Report Summary
DNA damage-induced cell death and DNA repair network
| Project/Area Number |
12143101
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Kiyoji Osaka University, Graduate School of Frontier Biosciences, Professor, 大学院・生命機能研究所, 教授 (80144450)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Mutsuo Biomolecular Engineering Research Institute, Director, 所長(研究職) (00037342)
YAMAIZUMI Masaru Kumamoto University School of Medicine, Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (70107093)
YASUI Akira Tohoku University, Institute of Development, Aging and Cancer, Professor, 加齢医学研究所, 教授 (60191110)
OGAWA Hideyuki Iwate College of Nursing, Professor, 教授 (70028207)
HANAOKA Fumio Osaka University, Graduate School of Frontier Biosciences, Professor, 大学院・生命機能研究所, 教授 (50012670)
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| Project Period (FY) |
2000 – 2005
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| Keywords | DNA damage / DNA repair / xeroderma pigmentosum / Cockayne syndrome / postreplication repair / knockout mice / nuclear matrix / transcription |
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| Research Abstract |
We isolated a novel protein complex XAB2 that interacts with Cockayne syndrome group A (CSA), QSB proteins and RNA polymerase II as well as xeroderma pigmentosum group A (XPA) protein and found that it is involved in transcription and transcription-coupled repair (TCR) and essential for mouse development. We purified the CSA protein as a multimeric protein complex that has a ubiquitin ligase activity. We produced four different kinds of XPG-targeted mice and showed that XPG gene is essential for mouse development and growth. The XPC/HR23B complex that is involved in global genome repair recognized and bound the structural abnormalities induced by DNA damage. It also bound thymine DNA glycosylase(TDG) and enhanced the TDG activity. DDB interacted with XPA protein on the damaged DNA and enhanced nucleotide excision repair(NER) activity in vitro. DDB acts prior to XPC in NER reactions. DNA polymerase eta responsible for XP variant form bypassed the DNA damage induced by active oxygen and alkylating agents as well as UV. We cloned human and mouse homologs of Rad18 involved in postreplication repair, and produced mRad18-deficient ES cells and mice that had a defect in post replication repair. We produced Nth1-knockout mice that are deficient in base excision repair of oxidative DNA damage but showednosignificant physiological abnormalities. However, three novel pyrimidine glycosylase activities were increased in the nucleus and mitochondria of the Nth1-deficient mice.
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