2006 Fiscal Year Final Research Report Summary
Function of human ORC (Origin Recognition Complex) in chromosome segregation and cytokinesis
| Project/Area Number |
16370079
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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 |
Molecular biology
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| Research Institution | HOKKAIDO UNIVERSITY (2006)
Kyoto University (2004-2005) |
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Principal Investigator |
OBUSE Chikashi Hokkaido Univ., Faculty of Advanced Life Science, Prof., 大学院先端生命科学研究院, 教授 (00273855)
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| Project Period (FY) |
2004 – 2006
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| Keywords | chromatin / replication / heterochromatin / ORC / telomere / mass spectrometry / proteomics / cell cycle |
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| Research Abstract |
ORC (Origin Recognition comple) is conserved among eukaryote, and essential for initiation of chromosomal replication. Recent studies suggest that ORC is involved in other cellular function, such as translation, chromosome segregation and cytokinesis, This research is aimed to uncover the molecular link between ORC and these cellular function other than chromosomal replication in human cells by proteomic approach.
Analysis of imunoprecipitates with ORC1 by proteomic approach using mass spectrometry found that ORC1 associates with ORC2, ORC3, ORC4 and ORC5. In addition to ORC subunits, it was revealed that constituents of telomere (TRF2, Rap 1), nuclear membrane (Sadl/Unc84) and uncharacterized WD40 protein (designated as ORC1BP1).
In relation to TRF2, it directly associates with ORC1 through myb-domain. This research showed that ORC and TRF2 interact with each other to achieve stable binding to telomere repeat. Knock down of ORC1 level by specific RNA interference induce telomere elongation, suggesting that ORC is involved in telomere homeostasis in human cells.
In relation to ORC1BP1, ORC1BP1 has Leu-rich repeat at its N-terminal half and WD40 repeat at its N-terminal half. This research showed that ORC1BP1 localized in nuclei and tightly associates with ORC1 and ORC2. Inhibition of ORC1BP1 by RNA interference cause prolonged period of G1 phase, indicated by reduction of BrdU and Cyclin B positive cells and increase of CDT1 positive cells. These results suggest that ORC1BP1 involved in G1 progression through direct interaction with ORC complex.
As described above, we could show some molecular links having ORC as its pivot which might be clues about explanation for ORC function in chromosome segregation and cycotkinesis.
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Research Products
(13 results)
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[Journal Article] Priming of Telophase Centromere for CENP-A Recruitment by Human hMis18α,β and M18BP.2007
Author(s)
Fujita, Y., Hayashi, T., Kiyomitsu, T., Toyoda, Y., Kokubu, A., Obuse.C., Yanagida, M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells.2006
Author(s)
Izuta, H., Ikeno, M., Suzuki, N., Tomonaga, T., Nozaki, N., Obuse.C., Kisu, Y., Goshima, N., Nomura, F., Nomura, N., Yoda, K.
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Journal Title
Genes Cells 11
Pages: 673-684
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two E3 ubiqutin ligase, SCF-Skp2 and DDB1-Cu14, target human Cdt1 for proteolysis.2006
Author(s)
Nishitani, H., Sugimoto, N., Roukos, V., Nakanishi, Y., Saijo, S., Obuse.C., Tsurimoto, T., Nakayama, K.I., Nakayama, K., Fujita, M., Lygerou, Z., Nishimoto, T.
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Journal Title
EMBO Journal 25
Pages: 1126-1136
Description
「研究成果報告書概要(欧文)」より
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