Rpd3L contributes to the DNA damage sensitivity of Saccharomyces cerevisiae checkpoint mutants Belén Gómez-González Harshil Patel Anne Early John FX Diffley 10779/crick.11365967.v1 https://crick.figshare.com/articles/journal_contribution/Rpd3L_contributes_to_the_DNA_damage_sensitivity_of_Saccharomyces_cerevisiae_checkpoint_mutants/11365967 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 EXO1 gene. Using a whole-genome sequencing approach, we identified two additional genes, RXT2 and RPH1, whose mutation can also partially suppress this DNA damage sensitivity. We provide evidence that RXT2 and RPH1 act in a common pathway, which is distinct from the EXO1 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. 2019-12-16 11:57:50 DNA damage checkpoint Rpd3L histone deacetylase replication replication fork arrest DNA Damage DNA Replication Histone Deacetylase 1 Histone Deacetylases Histone Demethylases Mutation Repressor Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Diffley FC001066 CB AS-ack 0604 Genetics Developmental Biology