Geminin, an inhibitor of DNA replication, is degraded during mitosis

Cell. 1998 Jun 12;93(6):1043-53. doi: 10.1016/s0092-8674(00)81209-x.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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 Proteins
  • Xenopus laevis

Substances

  • CDC6 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromatin
  • DNA, Complementary
  • GMNN protein, Xenopus
  • GMNN protein, human
  • Geminin
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Xenopus Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Ligases

Associated data

  • GENBANK/AF067855
  • GENBANK/AF067856
  • GENBANK/AF068780
  • GENBANK/AF068781