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
Hauptverfasser: McGarry, Thomas J, Kirschner, Marc W
Format: Artikel
Sprache:eng
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Zusammenfassung: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81209-X