The bur1-107 mutant delays G1/S transition and alleviates hydroxyurea sensitivity in checkpoint-deficient yeast.

In Saccharomyces cerevisiae, the cyclin-dependent kinase Bur1 is primarily known for its role in promoting transcription elongation, 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. Remarkably, bur1-107 alleviated the sensitivity ...
of mec1 and rad53 mutants to hydroxyurea (HU), suggesting that Bur1 activity becomes detrimental when checkpoint signaling is impaired. Furthermore, the bur1-107 mutation delayed the G1-to-S phase transition, implicating Bur1 as a key player in cell cycle progression. In HU-treated mec1 mutants, bur1-107 reduced ?-H2A accumulation, promoted S-phase resumption, and suppressed the formation of sub-G1 populations. Together, 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.
Genetics
Date: May. 30, 2025
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