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Related Experiment Videos

Cell cycle dependent regulation of the origin recognition complex.

Melvin L DePamphilis1

  • 1National Institute of Child Health and Human Development, Building 6, Room 3A-15, 9000 Rockville Pike, National Institutes of Health, Bethesda, Maryland 20892-2753, USA. depamphm@mail.nih.gov

Cell Cycle (Georgetown, Tex.)
|December 22, 2004
PubMed
Summary

The eukaryotic origin recognition complex (ORC) regulates DNA replication timing. Cell cycle modifications, including phosphorylation and ubiquitination, repress ORC activity, preventing DNA rereplication.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The eukaryotic origin recognition complex (ORC) is crucial for initiating DNA replication.
  • ORC selects replication origins and coordinates with cell cycle progression.
  • Understanding ORC regulation is key to preventing DNA rereplication.

Purpose of the Study:

  • To elucidate the cell cycle-dependent regulation of the origin recognition complex (ORC).
  • To identify the mechanisms by which ORC activity is repressed during specific cell cycle phases.
  • To establish the role of ORC modifications in preventing DNA rereplication.

Main Methods:

  • Comparative analysis of ORC function and regulation across diverse eukaryotic species (yeast, frogs, flies, mammals).
  • Investigation of cell cycle-dependent modifications of ORC subunits, including phosphorylation and ubiquitination.

Related Experiment Videos

  • Examination of the role of cyclin-dependent protein kinase [Cdk1(Cdc2)] in ORC inhibition.

    • Main Results:

    • ORC activity is repressed during S, G2, and M-phases through subunit modifications (phosphorylation, ubiquitination).
    • Cyclin-dependent protein kinase [Cdk1(Cdc2)] inhibits functional ORC/chromatin site assembly.
    • ORC or its Orc1 subunit exhibits differential chromatin binding dynamics during cell division in metazoa compared to yeast.

    Conclusions:

    • The "ORC cycle," involving cell cycle-dependent modifications and regulated chromatin association, is essential for preventing DNA rereplication.
    • ORC regulation is a conserved mechanism across eukaryotes, ensuring genomic stability.
    • Mitotic kinase activity directly impacts ORC function, linking replication control to cell division progression.