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A group of interacting yeast DNA replication genes
1Department of Genetics, Stanford University, California 94305.
Genes & Development
|June 1, 1991
Summary
Mutations in cell division cycle genes CDC46 and CDC47 are linked to DNA replication initiation. These gene mutations cause chromosome instability and cell cycle arrest, revealing a new gene family essential for DNA replication.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cell division cycle genes CDC46 and CDC47 were identified as suppressors of mutations in CDC45 and CDC54.
- Genetic interactions between these genes suggest they function as a group.
Purpose of the Study:
- To investigate the role of CDC46, CDC47, CDC45, and CDC54 in DNA replication and cell cycle progression.
- To characterize the consequences of mutations in these genes on chromosome stability and DNA synthesis.
Main Methods:
- Genetic analysis of mutation combinations (allele-specific suppression, synthetic lethality).
- Analysis of chromosome loss, recombination, and damage using chromosome electrophoresis.
- Conditional mutant analysis to assess cell cycle progression.
Main Results:
- Mutations in CDC46, CDC47, CDC45, and CDC54 are involved in early DNA replication, likely initiation.
- Defective mutants exhibit high rates of mitotic chromosome loss and recombination, and accumulate chromosome damage.
- Conditional mutants arrest at the start of DNA synthesis or later in S-phase.
Conclusions:
- The studied genes form a genetically interacting group essential for DNA replication initiation.
- CDC46 protein belongs to a newly identified gene family conserved across species (yeast and mouse) and crucial for DNA initiation.