2004 Fiscal Year Final Research Report Summary
Characterization ofgenes involved in genomic stability using an experinental model organism.
| Project/Area Number |
13214008
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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 | Tohoku University |
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Principal Investigator |
HIGASHITANI Atsushi Graduate School ofLife Sciences, Ppofessor, 生命科学研究科, 教授 (40212162)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Checkpoint control / DNA repair / Ubiquitin / Cell cycle / Chromosomal aberration / Radiation / DNA damage / ataxia |
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| Research Abstract |
Many human cancers originate from defects in the DNA damage response and the cell cycle control. These defects cause instability of chromosomes. To identify and characterize novel genes of DNA damage response and the cell cycle control, we used an experimental model organism the nematode Caenorthabditis elegans.
In eukaryotic cells, members of the ataxia telangiectasia mutated gene (ATM) family play important roles in conserved signal transduction pathways for the DNA damage response. We have identified an ATM-like Ce-atl-1 in the C. elegans genome. Depletion of its gene product by RNA-mediated interference (RNA1) caused pronounced defects in chromosomal segregation and DNA damage responses such as repair, apoptosis, and G1 arrest From the results of yeast two-hybrid analysis, its N-terminal half physically interacted with PCNA and its C-terminal half interacted with several gene products related to transport of ER, endocytosis, transcriptional factor, single strand binding protein SSB.
… More
Some of them were essential for apoptosis, but dispensable for DNA repair process.
We also analyzed the Ring-H2 finger protein RBX1 that is a common subunit of SKP1-CDC53/CUL1-F box (SCF), other Cullins and von Hippel-Lindau (VHL) tumour suppressor E3 ubiquitin ligase complexes. The RBX1 RNAi experiment suggested that the RBX1 protein participates in diverse functions relevant to mitotic chromosomal condensation and segregation, G1/S progression and cytokinesis. All these defects of RB×1 RNAi were consistent with those found after either depletion of CUL2, Elongin B (ELB1) or Elongin C (ELC1). In addition, direct interactions between ELC1 and CUL2, and ELC1 and ELC2, respectively, were revealed by bacterial two-hybrid analysis. Thus, the RB×1/CUL2/ELC1/ELB1 complex acts as an E3 ubiquitin ligase in C. elegans and is essential for diverse functions relevant to chromosomal dynamics and cell cycle control. These phenomena are probably ubiquitous in human cancer, because all these genes identified in this study are highly conserved in mammals. Less
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[Journal Article] Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis.2003
Author(s)
Sasagawa, Y., Urano, T., Kohara, Y., Takahashi, H., Higashitani, A.
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Journal Title
Genes Cells 8
Pages: 857-872
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Efficient repair of DNA damage induced by heavy ion particles in meiotic prophase I nuclei of Caenorhabditis elegans.2003
Author(s)
Takanami, T., Zhang, Y., Aoki, H., Abe, T., Yoshida, S., Takahashi, H., Horiuchi, S., Higashitani, A.
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Journal Title
J. Radiation Research 44
Pages: 271-276
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis.2003
Author(s)
Sasagawa, Y., Urano, T., Kohara, Y., Takahashi, H., Higashitani, A.
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Journal Title
Genes to Cells 8
Pages: 857-872
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Efficient repair of DNA damage induced by heavy ion particles in meiotic prophase I nuclei of Caenorhabditis elegans.2003
Author(s)
Takanami, T., Zhang, Y, Aoki, H., Abe, T., Yoshida, S., Takahashi, H., Horiuchi, S., Higashitani, A.
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Journal Title
J.Radiation Research 44
Pages: 271-276
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis elegans.2000
Author(s)
Aoki, H., Sato, S., Takanami, T., Ishihara, T., Katsura, I., Takahashi, H., Higashitani, A.
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Journal Title
Molecular General Genetics 264
Pages: 119-126
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Caenorhabditis elegans Chk2-like gene is essential for meiosis but dispensable for DNA repair.2000
Author(s)
Higashitani, A., Aoki, H., Mori, A., Sasagawa, Y., Takanami, T., Takahashi, H.
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Journal Title
FEBS Letters 485
Pages: 35-39
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis elegans.2000
Author(s)
Aoki, H., Sato, S., Takanami, T, Ishihara, T., Katsura, I, Takahashi, H., Higashitani, A.
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Journal Title
Molecular General Genetics 264
Pages: 119-126
Description
「研究成果報告書概要(欧文)」より
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