Cdc6 and DNA replication: limited to humble origins

Area of Science:

• Cell biology
• Molecular biology
• Genetics

Background:

• The Cdc6 protein in budding yeast is crucial for the initiation of DNA replication.
• Mutations in Cdc6 (cdc6-1) lead to unreplicated DNA and increased minichromosome loss.
• Overexpression of a related protein, Cdc18, in fission yeast causes DNA rereplication, but Cdc6 overexpression does not.

Purpose of the Study:

• To further define the specific role of the budding yeast Cdc6 protein in DNA replication.
• To investigate the mechanisms limiting Cdc6p's function to the G1 phase of the cell cycle.

Main Methods:

• Analysis of cdc6-1 mutants.
• Studies on the effects of Cdc6p overexpression.
• Investigation of Cdc6p protein stability and localization.

Main Results:

• Cdc6p promotes DNA replication exclusively from the end of mitosis until late G1.
• Cdc6p is highly unstable within the cell.
• Neither protein degradation nor precise nuclear localization is essential for restricting DNA replication to the G1 phase.

Conclusions:

• The temporal regulation of DNA replication initiation by Cdc6p is independent of its degradation or nuclear import.
• Cdc6p's function is tightly controlled to occur only during the specific window between mitosis and late G1.