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

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Harshil Patel^2¹  Belén Gómez-González^1² 

[1]Bioinformatics and Biostatistics, The Francis Crick Institute, NW1 1AT London, UK^2

[2]Chromosome Replication Laboratory, The Francis Crick Institute, NW1 1AT London, UK^1

关键词: DNA damage checkpoint;    replication fork arrest;    Rpd3L;    histone deacetylase;    replication;   

DOI  :  10.1534/genetics.118.301817

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

CC BY