The ORC1 cycle in human cells

II. Dynamic changes in the human ORC complex during the cell cycle

Satoshi Ohta, Yasutoshi Tatsumi, Masatoshi Fujita, Toshiki Tsurimoto, Chikashi Obuse

研究成果: ジャーナルへの寄稿記事

58 引用 (Scopus)

抄録

The origin recognition complex (ORC) plays a central role in regulating the initiation of DNA replication in eukaryotes. The level of the ORC1 subunit oscillates throughout the cell cycle, defining an ORC1 cycle. ORC1 accumulates in G1 and is degraded in S phase, although other ORC subunits (ORCs 2-5) remain at almost constant levels. The behavior of ORC components in human cell nuclei with respect to the ORC1 cycle demonstrates that ORCs 2-5 form a complex that is present throughout the cell cycle and that associates with ORC1 when it accumulates in G1 nuclei. ORCs 2-5 are found in both nuclease-insoluble and -soluble fractions. The appearance of nuclease-insoluble ORCs 2-5 parallels the increase in the level of ORC1 associating with nuclease-insoluble, non-chromatin nuclear structures. Thus, ORCs 2-5 are temporally recruited to nuclease-insoluble structures by formation of the ORC1-5 complex. An artificial reduction in the level of ORC1 in human cells by RNA interference results in a shift of ORC2 to the nuclease-soluble fraction, and the association of MCM proteins with chromatin fractions is also blocked by this treatment. These results indicate that ORC1 regulates the status of the ORC complex in human nuclei by tethering ORCs 2-5 to nuclear structures. This dynamic shift is further required for the loading of MCM proteins onto chromatin. Thus, the pre-replication complex in human cells may be regulated by the temporal accumulation of ORC1 in G1 nuclei.

元の言語英語
ページ(範囲)41535-41540
ページ数6
ジャーナルJournal of Biological Chemistry
278
発行部数42
DOI
出版物ステータス出版済み - 10 17 2003

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Origin Recognition Complex
Cell Cycle
Cells
Chromatin
Multicarrier modulation
RNA Interference
Eukaryota
Cell Nucleus
DNA Replication
S Phase
Proteins
Association reactions
RNA
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry

これを引用

The ORC1 cycle in human cells : II. Dynamic changes in the human ORC complex during the cell cycle. / Ohta, Satoshi; Tatsumi, Yasutoshi; Fujita, Masatoshi; Tsurimoto, Toshiki; Obuse, Chikashi.

:: Journal of Biological Chemistry, 巻 278, 番号 42, 17.10.2003, p. 41535-41540.

研究成果: ジャーナルへの寄稿記事

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abstract = "The origin recognition complex (ORC) plays a central role in regulating the initiation of DNA replication in eukaryotes. The level of the ORC1 subunit oscillates throughout the cell cycle, defining an ORC1 cycle. ORC1 accumulates in G1 and is degraded in S phase, although other ORC subunits (ORCs 2-5) remain at almost constant levels. The behavior of ORC components in human cell nuclei with respect to the ORC1 cycle demonstrates that ORCs 2-5 form a complex that is present throughout the cell cycle and that associates with ORC1 when it accumulates in G1 nuclei. ORCs 2-5 are found in both nuclease-insoluble and -soluble fractions. The appearance of nuclease-insoluble ORCs 2-5 parallels the increase in the level of ORC1 associating with nuclease-insoluble, non-chromatin nuclear structures. Thus, ORCs 2-5 are temporally recruited to nuclease-insoluble structures by formation of the ORC1-5 complex. An artificial reduction in the level of ORC1 in human cells by RNA interference results in a shift of ORC2 to the nuclease-soluble fraction, and the association of MCM proteins with chromatin fractions is also blocked by this treatment. These results indicate that ORC1 regulates the status of the ORC complex in human nuclei by tethering ORCs 2-5 to nuclear structures. This dynamic shift is further required for the loading of MCM proteins onto chromatin. Thus, the pre-replication complex in human cells may be regulated by the temporal accumulation of ORC1 in G1 nuclei.",
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