2004 Fiscal Year Final Research Report Summary
Analysis of a novel back-up repair system for UV-induced DNA damage in human cells.
| Project/Area Number |
15310036
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Kanazawa University, Graduate School of Natural Science and Technology |
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Principal Investigator |
MATSUNAGA Tsukasa Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Professor, 自然科学研究科, 教授 (60192340)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGAKI Yasuhito Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Research Associate, 自然科学研究科, 助手 (20232275)
WAKASUGI Mitsuo Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Research Associate, 自然科学研究科, 助手 (80345595)
YAMASHITA Katsumi Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Associate Professor, 自然科学研究科, 助教授 (10191280)
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| Project Period (FY) |
2003 – 2004
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| Keywords | DNA damage / nucleotide excision repair / ultraviolet light / cyclobutane pyrimidine dimer / (6-4) photoproduct / xeroderma pigmentosum / knock-out mouse / adaptive response |
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| Research Abstract |
We have established a super-sensitive detection method for measuring cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs) induced by biological doses of ultraviolet (UV) light and suggested that human cells might have a novel repair system mainly for 6-4PPs other than nucleotide excision repair which has been thought to be only repair system for those lesions in humans so far. In this study, we have obtained the following findings.
1.The removal of 6-4PPs was observed even in the embryonic fibroblasts derived from xpa(-/-) or xpg(-/-) knock-out mice (30-50% after 24 hr). In addition, the removal of CPDs was also detected in those cells with a less efficiency (20-30% after 48 hr).
2.HeLa cells stably expressing AlwNI-type mutant XPA did not show any impairment of nucleotide excision repair activity, suggesting that this mutant XPA protein does not have a dominant-negative effect.
3.We have further sensitized the detection method for CPDs, enabling us to determine the repair kinetics of CPDs in cells exposed to non-killing doses of Was low as 0.1 J/m^2. Under this condition, we have found that xeroderma pimentosum cells significantly remove CPDs (〜40% after 48hr).
4.We could observe some weak enhancement of repair efficiency after UV irradiation of 1 J/m^2 when the human cells had been pie-exposed to 0.2 J/m^2. However, we need more extensive experiments to conclude whether the back-up repair system is under the control of adaptive responses.
Taken together with those results, we concluded that mammalian cells have a certain back-up repair system, independent of XPA and XPG, which removes mainly 6-4PP but also CPDs with a less efficiency.
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Author(s)
Mori, M., Yoshida, K., Ishigaki, Y., Matsunaga, T., Nikaido, O., Kameda, K., Kondo, T.
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Journal Title
Bioorg.Med.Chem. 13
Pages: 2015-2020
Description
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[Journal Article] Characterization of pathways dependent on the uvde, uvrA1, or uvrA2 gene product for ultraviolet resistance in Deinococcus radiodurans.2005
Author(s)
Tanaka, M., Narumi, I., Funayama, T., Kikuchi, M., Watanabe, H., Matsunaga, T., Nikaido, O., Yamamoto, K.
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Journal Title
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[Journal Article] Functional and physical interactions between ERCC1 and MSH2 for resistance to cis-platinum in mammalian cells.2004
Author(s)
Lan, L., Rabeya, R.M., Hayashi, T., Nakajima, S., Kanno, S., Takao, M., Matsunaga, T., Yoshino, M., Ichikawa, M., te Riele, H., Tsuchiya, S., Tanaka, K., Yasui, A.
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Journal Title
DNA Repair 3
Pages: 135-143
Description
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[Journal Article] Nuclear export signal in CDC25B.2004
Author(s)
Uchida, S., Ohtsubo, M., Shimura, M., Hirata, M., Nakagama, H., Matsunaga, T., Yoshida, M., Ishizaka, Y., Yamashita, K.
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Journal Title
Biochem.Biophys.Res.Commun. 316
Pages: 226-232
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[Journal Article] Identification of the XPG region that causes the onset of Cockayne syndrome by using Xpg mutant mice generated by the cDNA-mediated knock-in method.2004
Author(s)
Shiomi, N., Kito, S., Oyama, M., Matsunaga, T., Harada, Y.-N., Ikawa, M., Okabe, M., Shiomi, T.
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Journal Title
Mol.Cell.Biol. 24
Pages: 3712-3719
Description
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[Journal Article] Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B : binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B.2004
Author(s)
Uchida, S., Kuma, A., Ohtsubo, M., Shimura, M., Hirata, M., Nakagama, H., Matsunaga, T., Ishizaka, Y., Yamashita K.
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Journal Title
J.Cell Sci. 117
Pages: 3011-3020
Description
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[Journal Article] Human NTH1 physically interacts with p53 and proliferating cell nuclear antigen.2004
Author(s)
Oyama, M., Wakasugi, M., Hama, T., Hashidume, H., Iwakami, Y., Imai, R., Hoshino, S., Morioka, H., Ishigaki, Y., Nikaido, O., Matsunaga, T.
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Journal Title
Biochem.Biophys.Res.Commun. 321
Pages: 183-191
Description
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[Journal Article] A gene for a Class II DNA photolyase from Oryza sativa : cloning of the cDNA by dilution-amplification.2003
Author(s)
Hirouchi, T., Nakajima, S., Najrana, T., Tanaka, M., Matsunaga, T., Hidema, J., Teranishi, M., Fujino, T., Kumagai, T., Yamamoto, K.
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Journal Title
Mol.Gen.Genomics 269
Pages: 508-516
Description
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[Journal Article] Disruption of the AtREV3 gene causes hypersensitivity to ultraviolet B light and γ-rays in Arabidopsis inplication of the presence of a translesion synthesis mechanism in plants.2003
Author(s)
Sakamoto, A., Lan, V.T.T., Hase, Y., Shikazono, N., Matsunaga, T., Tanaka, A.
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Journal Title
Plant Cell 15
Pages: 2042-2057
Description
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