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.
Pubmed ID: 9635433 RIS Download
Mesh terms: Amino Acid Sequence | Anaphase-Promoting Complex-Cyclosome | Animals | Cell Cycle Proteins | Cell Division | Cell Nucleus | Chromatin | DNA Replication | DNA, Complementary | Geminin | HeLa Cells | Humans | Ligases | Mitosis | Molecular Sequence Data | Molecular Weight | Nuclear Proteins | Recombinant Fusion Proteins | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Ubiquitin-Protein Ligase Complexes | Ubiquitin-Protein Ligases | Ubiquitins | Xenopus Proteins | Xenopus laevis
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