Rpd3L contributes to the DNA damage sensitivity of Saccharomyces cerevisiae checkpoint mutants

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Abstract

DNA replication forks that are stalled by DNA damage activate an S-phase checkpoint that prevents irreversible fork arrest and cell death. The increased cell death caused by DNA damage in budding yeast cells lacking the Rad53 checkpoint protein kinase is partially suppressed by deletion of the gene. Using a whole-genome sequencing approach, we identified two additional genes, and , whose mutation can also partially suppress this DNA damage sensitivity. We provide evidence that and act in a common pathway, which is distinct from the pathway. Analysis of additional mutants indicates that suppression works through the loss of the Rpd3L histone deacetylase complex. Our results suggest that the loss or absence of histone acetylation, perhaps at stalled forks, may contribute to cell death in the absence of a functional checkpoint.