Bur1-driven G1-to-S phase transition induces hydroxyurea sensitivity in yeast checkpoint mutants

In Saccharomyces cerevisiae, the cyclin-dependent kinase Bur1 is known for its role in promoting transcription elongation and histone modifications, thereby regulating gene expression. In this study, we investigated the genetic interactions between a hypomorphic BUR1 allele (bur1-107) and null mutants of the checkpoint kinases Mec1 and Rad53. Our findings show that the bur1-107 allele suppresses hydroxyurea (HU) sensitivity in mec1 and rad53 mutants, indicating that Bur1 activity may be detrimental in the absence of functional checkpoint signaling. Additionally, the bur1-107 mutation delays the G1-to-S phase transition, indicating a key role for Bur1 in cell cycle progression. Notably, bur1-107 reduces {gamma}-H2A accumulation, facilitates S-phase resumption, and supresses the sub-G1 population in HU-treated mec1 mutants. These findings suggest that Bur1-driven G1-to-S phase progression exacerbates DNA damage and cell death in checkpoint-deficient cells exposed to HU. This study highlights a novel role for Bur1 in modulating the cellular response to replication stress in checkpoint-compromised cells.