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Cell cycle regulation of DNA replication initiator factor Dbf4p
L Cheng1, T Collyer, C F Hardy
1Department of Cell Biology and Physiology and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Molecular and Cellular Biology
|May 18, 1999
Summary
The cell cycle regulator Dbf4p is crucial for DNA replication initiation and its levels are tightly controlled. Dbf4p is also modified by DNA damage pathways, linking it to mitosis completion.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Eukaryotic DNA replication is a tightly regulated process, occurring once per cell cycle.
- Initiation of DNA replication requires cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p/Dbf4p kinases.
- The cell cycle-dependent regulation of Dbf4p, a key replication initiator, is not fully understood.
Purpose of the Study:
- To investigate the cell cycle regulation of Dbf4p levels.
- To explore the relationship between Dbf4p, DNA damage response, and the anaphase-promoting complex (APC).
- To elucidate the role of Dbf4p in mitosis progression.
Main Methods:
- Cell cycle analysis to monitor Dbf4p levels.
- Mutation analysis of anaphase-promoting complex (APC) components.
- Investigation of Dbf4p modification in response to DNA damage.
- Exploration of Dbf4p interaction with Cdc5p.
Main Results:
- Dbf4p levels are cell cycle regulated, increasing during S phase and mitosis, then declining.
- Dbf4p levels are sensitive to mutations in APC components.
- Dbf4p undergoes modification in response to DNA damage, dependent on the DNA damage response pathway.
- Dbf4p interacts with Cdc5p, an M phase regulator of the APC.
Conclusions:
- Dbf4p acts as a crucial link between DNA replication initiation and the completion of mitosis.
- Dbf4p's regulation by the APC and DNA damage pathways suggests its involvement in coordinating cell cycle events.
- Further research into Dbf4p's role during mitosis is warranted.