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Think global, act local--how to regulate S phase from individual replication origins
1Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique (UMR 5535) & Université Montpellier II, Montpellier, F-34293, France. Pasero@igm.cnrs-mop.fr
Current Opinion in Genetics & Development
|April 8, 2000
Summary
Eukaryotic DNA replication origins use conserved proteins but divergent DNA sequences. The origin recognition complex (ORC) binds specific sites, enabling conserved initiation factors to assemble on varied replication origins. This process is regulated by kinases, influencing DNA replication patterns and epigenetic states.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Eukaryotes utilize conserved proteins for replication origin licensing, yet origin DNA sequences show significant divergence.
- The Origin Recognition Complex (ORC) plays a crucial role in initiating DNA replication across eukaryotes.
Purpose of the Study:
- To investigate the divergence of DNA-binding activity within the ORC.
- To understand how conserved initiation factors are recruited to polymorphic replication origins.
- To elucidate the regulatory mechanisms controlling DNA replication initiation and epigenetic state establishment.
Main Methods:
- Identification of specific ORC binding sites on fission yeast and Drosophila chromosomes.
- Analysis of the DNA-binding activity of the ORC.
- Investigation of cyclin- and Dbf4-dependent kinase roles in origin activation and S phase control.
Main Results:
- Specific ORC binding sites were identified on fission yeast and Drosophila chromosomes.
- Evidence suggests ORC's DNA-binding activity has diverged to recruit conserved initiation factors on polymorphic origins.
- Dbf4-dependent kinases regulate S phase at the level of individual origins, distinct from cyclin-dependent kinases.
Conclusions:
- The divergence in ORC DNA-binding activity facilitates the recruitment of conserved initiation factors to diverse replication origins.
- Differential regulation of origins by kinases contributes to specific DNA replication patterns.
- These replication patterns are integral to establishing epigenetic chromosome states.