Rpd3L Contributes to the DNA Damage Sensitivity of Saccharomyces cerevisiae Checkpoint Mutants

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• DNA replication forks are vulnerable to damage, activating S-phase checkpoints to prevent cell death.
• Budding yeast lacking the Rad53 checkpoint protein kinase exhibit increased sensitivity to DNA damage.

Purpose of the Study:

• To identify novel genes that suppress DNA damage sensitivity in yeast mutants lacking the Rad53 checkpoint protein kinase.
• To elucidate the pathways and mechanisms involved in DNA damage-induced cell death suppression.

Main Methods:

• Whole-genome sequencing to identify suppressor genes.
• Genetic analysis of mutant strains.
• Investigation of histone deacetylase complex involvement.

Main Results:

• Deletion of EXO1 partially suppresses DNA damage sensitivity.
• Mutations in RXT2 and RPH1 also partially suppress DNA damage sensitivity, acting via a distinct pathway from EXO1.
• Suppression is linked to the loss of the Rpd3L histone deacetylase complex.

Conclusions:

• RXT2 and RPH1 represent novel suppressors of DNA damage sensitivity in budding yeast.
• The Rpd3L histone deacetylase complex plays a role in DNA damage-induced cell death.
• Loss of histone acetylation at stalled replication forks may contribute to cell death when the checkpoint is absent.