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S-phase cyclins are required for a stable arrest at metaphase
1Howard Hughes Medical Institute and Department of Genetics, University of Pennsylvania Medical School, Room 445 CRB, 415 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
Current Biology : CB
|January 4, 2001
Summary
S-phase cyclins Clb5 and Clb6 are essential for the DNA damage checkpoint in yeast, preventing premature cell division. Their absence leads to checkpoint bypass and genomic instability.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- A critical DNA damage checkpoint in Saccharomyces cerevisiae halts mitosis at metaphase.
- This checkpoint ensures genomic integrity by preventing cell division until DNA damage is repaired.
Purpose of the Study:
- To investigate the role of S-phase cyclins Clb5 and Clb6 in the DNA damage checkpoint.
- To determine the mechanism by which these cyclins maintain the metaphase arrest.
Main Methods:
- Utilized Saccharomyces cerevisiae (yeast) as a model organism.
- Employing methyl methanesulfonate (MMS) to induce DNA damage.
- Analyzing cell cycle progression, checkpoint control, and protein levels (Pds1) in wild-type and mutant strains.
Main Results:
- Strains lacking Clb5 and Clb6 (clb5 clb6 mutants) are hypersensitive to DNA damage.
- Over 50% of clb5 clb6 mutants bypassed the metaphase checkpoint after MMS treatment, arresting with separated sister chromatids.
- clb5 clb6 mutants underwent nuclear division despite the presence of Pds1, an anaphase inhibitor, suggesting a failure in maintaining sister chromatid cohesion.
Conclusions:
- S-phase cyclins Clb5 and Clb6 are required for the DNA damage-induced metaphase arrest in yeast.
- These cyclins likely play a novel role in maintaining sister chromatid cohesion during metaphase arrest, possibly by regulating Pds1 activity.