Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis
We describe a novel 25 kDa protein, geminin, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin has a destruction box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In synchronized HeLa cells, geminin is absent during G1 phase...
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| Veröffentlicht in: | Cell 1998-06, Vol.93 (6), p.1043-1053 |
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| creator | McGarry, Thomas J Kirschner, Marc W |
| description | We describe a novel 25 kDa protein, geminin, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin has a destruction box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase–anaphase transition. Geminin inhibits DNA replication by preventing the incorporation of MCM complex into prereplication complex (pre-RC). We propose that geminin inhibits DNA replication during S, G2, and M phases and that geminin destruction at the metaphase–anaphase transition permits replication in the succeeding cell cycle. |
| doi_str_mv | 10.1016/S0092-8674(00)81209-X |
| format | Article |
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Geminin has a destruction box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase–anaphase transition. Geminin inhibits DNA replication by preventing the incorporation of MCM complex into prereplication complex (pre-RC). 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Geminin has a destruction box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase–anaphase transition. Geminin inhibits DNA replication by preventing the incorporation of MCM complex into prereplication complex (pre-RC). We propose that geminin inhibits DNA replication during S, G2, and M phases and that geminin destruction at the metaphase–anaphase transition permits replication in the succeeding cell cycle.</description><subject>Amino Acid Sequence</subject><subject>Anaphase-Promoting Complex-Cyclosome</subject><subject>Animals</subject><subject>Cell Cycle Proteins - chemistry</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Division</subject><subject>Cell Nucleus - chemistry</subject><subject>Chromatin - metabolism</subject><subject>DNA Replication - physiology</subject><subject>DNA, Complementary - genetics</subject><subject>Geminin</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Ligases - metabolism</subject><subject>Mitosis - physiology</subject><subject>Molecular Sequence Data</subject><subject>Molecular Weight</subject><subject>Nuclear Proteins - metabolism</subject><subject>Recombinant Fusion Proteins</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Sequence Homology, Amino Acid</subject><subject>Ubiquitin-Protein Ligase Complexes</subject><subject>Ubiquitin-Protein Ligases</subject><subject>Ubiquitins - metabolism</subject><subject>Xenopus laevis</subject><subject>Xenopus Proteins</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkElLAzEUx4MotS4foTAnUXD0ZbJNTlKsS8EFXKC3kCZvNNLO1GQq-O0d2-LV0zu83_8tP0IGFM4oUHn-DKCLvJSKHwOclLQAnU-2SJ-CVjmnqtgm_T9kl-yl9AEApRCiR3paMsEZ65PRDc5DHerTzNbZuH4P09A2MWuqbPQwzJ5wMQvOtqHpgHHKRvgWrUef-WUM9Vt238EppAOyU9lZwsNN3Sev11cvl7f53ePN-HJ4lzshZJuXzNlSW0k55bKqKucLzzinWHjNWNHdVk0Fl6WFUnkPnqEXyFSldKEE-ILtk6P13EVsPpeYWjMPyeFsZmtslskorbmm3WP_gVRyJaSSHSjWoItNShErs4hhbuO3oWB-NZuVZvPr0ACYlWYz6XKDzYLldI7-L7Xx2vUv1n3sdHwFjCa5gLVDHyK61vgm_LPhB3wPipw</recordid><startdate>19980612</startdate><enddate>19980612</enddate><creator>McGarry, Thomas J</creator><creator>Kirschner, Marc W</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>19980612</creationdate><title>Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis</title><author>McGarry, Thomas J ; Kirschner, Marc W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-83ca89a614146fffcd2d3441e2d9332085fb5468a087dd0d3ed5e37f792750d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Amino Acid Sequence</topic><topic>Anaphase-Promoting Complex-Cyclosome</topic><topic>Animals</topic><topic>Cell Cycle Proteins - chemistry</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Division</topic><topic>Cell Nucleus - chemistry</topic><topic>Chromatin - metabolism</topic><topic>DNA Replication - physiology</topic><topic>DNA, Complementary - genetics</topic><topic>Geminin</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Ligases - metabolism</topic><topic>Mitosis - physiology</topic><topic>Molecular Sequence Data</topic><topic>Molecular Weight</topic><topic>Nuclear Proteins - metabolism</topic><topic>Recombinant Fusion Proteins</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Sequence Homology, Amino Acid</topic><topic>Ubiquitin-Protein Ligase Complexes</topic><topic>Ubiquitin-Protein Ligases</topic><topic>Ubiquitins - metabolism</topic><topic>Xenopus laevis</topic><topic>Xenopus Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McGarry, Thomas J</creatorcontrib><creatorcontrib>Kirschner, Marc W</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McGarry, Thomas J</au><au>Kirschner, Marc W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>1998-06-12</date><risdate>1998</risdate><volume>93</volume><issue>6</issue><spage>1043</spage><epage>1053</epage><pages>1043-1053</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>We describe a novel 25 kDa protein, geminin, which inhibits DNA replication and is degraded during the mitotic phase of the cell cycle. Geminin has a destruction box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase–anaphase transition. Geminin inhibits DNA replication by preventing the incorporation of MCM complex into prereplication complex (pre-RC). We propose that geminin inhibits DNA replication during S, G2, and M phases and that geminin destruction at the metaphase–anaphase transition permits replication in the succeeding cell cycle.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9635433</pmid><doi>10.1016/S0092-8674(00)81209-X</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| subjects | Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome Animals Cell Cycle Proteins - chemistry Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Division Cell Nucleus - chemistry Chromatin - metabolism DNA Replication - physiology DNA, Complementary - genetics Geminin HeLa Cells Humans Ligases - metabolism Mitosis - physiology Molecular Sequence Data Molecular Weight Nuclear Proteins - metabolism Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases Ubiquitins - metabolism Xenopus laevis Xenopus Proteins |
| title | Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis |
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