1998 Fiscal Year Final Research Report Summary
Molecular Mechanisms of DNA Damage Recoguition and Repair
| Project/Area Number |
08407072
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
HANAOKA Fumio Osaka Univ., IMCB,Professor, 細胞生体工学センター, 教授 (50012670)
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| Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Takafumi Osaka Univ.IMCB,Research Assistant, 細胞生体工学センター, 助手 (90273721)
MASUTANI Chikahide Osaka Univ.IMCB,Research Assistant, 細胞生体工学センター, 助手 (40241252)
OHKUMA Yoshiaki Osaka Univ.IMCB,Associate Professor, 細胞生体工学センター, 助教授 (70192515)
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| Project Period (FY) |
1996 – 1998
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| Keywords | DNA repair / NER / xeroderma pigmentosum / XPC protein / Vpr protein / HHR23B protein / 26S proteasome / S5a protein |
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| Research Abstract |
We previously isolated a protein complex which biochemically corrects the defect of XP-C cell extracts in nucleotide excision repair (NER) in vitro. In the present study, we have analyzed the functions of the protein complex, XPC/HHR23B, in NER in mammalian cells and obtained the following results.
1) In mouse cells, there are homologues of human XPC/HHR23B and another RAD23 homologue, HHR23A.They have quite high homologies with each other.
2) We found most of XPC, HHR23B and HHR23A in nucleus. They do not make a tight complex with other NER proteins.
3) HHR23B stimulates the NER activity of XPC protein in vitro.
4) HHR23A protein makes a complex with HIV-1 Vpr protein and affects the cell cycle progression.
5) A very limited region of HHR23B is necessary and sufficient for XPC binding as well as the stimulation of NER activity of XPC.
6) HHR23A could reconstitute a physical complex with XPC and stimulate the in vitro repair activity in place of HHR23B.
7) XPC/HHR23B complex works as the earliest damage detector to initiate global genome repair subpathway of NER.
8) We found that a component of 26S proteasome, S5a, associates with HHR23B in yeast two-hybrid system as well as in crude cell extracts.
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[Publications] Sugasawa, K., Masutani, C., Uchida, A., Maekawa, T., van der Spek, P.J., Bootsma, D., Hoeijmakers, J.H., J., and Hanaoka, F.: "HHR23B,a human Rad23 homolog, stimulates XPC protein in nucleotide excision repair in uitro." Mol.Cell.Biol.16. 4852-4861 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] van der Spek, P.J., Eker, A., Rademakers, S., Visser, C., Sugasawa K., Masutani, C., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.: "XPC and human homologs of RAD23 : intracellular localization and relationship to other nucleotide excision repair complexes." Nucl.Acids Res.24. 2551-2559 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Witheres-Ward, E.S., Jowett, J.B., Stewart, S.A., Xie, Y.M., Garfinkel, A., Shibagaki, Y., Chow, S.A., Shah, N., Hanaoka, F., Sawitz, D,G., Armstrong, R.W., Souza, L.M., and Chen, I.S.: "Human immunodeficiency virus type 1 Vpr interacts with HHR23A,a cellular protein implicated in nucleotide excision DNA repair." J.Virol.71. 9732-9742 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Masutani, C., Araki, M., Sugasawa, K., van der Spek, P.J., Yamada, A., Uchida, A., Maekawa, T., Bootsma, D., Hoeijmakers, J.H.J., and Hanaoka, F.: "Identification and characterization of XPC-binding domain of hHR23B." Mol.Cell.Biol.17. 6915-6923 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sugasawa, K., Ng, J.M.Y., Masutani, C., Maekawa, T., Uchida, A., van der Spek, P.J., Eker, A.P.M., Rademakers, S., Visser, C., Aboussekhra, A., Wood, R.D., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.: "Two human homologues of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity." Mol.Cell.Biol.17. 6924-6931 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sugasawa, K., Ng, J.M.Y., Masutani, C., Iwai, S., van der Spek, P., Eker, A.P.M., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.: "Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair." Mol.Cell.2. 223-232 (1998)
Description
「研究成果報告書概要(欧文)」より
