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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Division
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Cell Nucleus / chemistry
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Chromatin / metabolism
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DNA Replication / physiology*
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DNA, Complementary / genetics
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Geminin
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HeLa Cells
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Humans
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Ligases / metabolism
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Mitosis / physiology*
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Molecular Sequence Data
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Molecular Weight
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Nuclear Proteins / metabolism
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Ubiquitin-Protein Ligase Complexes*
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism
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Xenopus Proteins
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Xenopus laevis
Substances
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CDC6 protein, S cerevisiae
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Cell Cycle Proteins
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Chromatin
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DNA, Complementary
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GMNN protein, Xenopus
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GMNN protein, human
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Geminin
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Nuclear Proteins
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Ubiquitins
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Xenopus Proteins
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Ubiquitin-Protein Ligases
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Ligases
Associated data
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GENBANK/AF067855
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GENBANK/AF067856
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GENBANK/AF068780
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GENBANK/AF068781