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

IF 3.3 3区 生物学 Q2 GENETICS & HEREDITY
Genetics Pub Date : 2025-05-30 DOI:10.1093/genetics/iyaf104
Stefany Cristine Rodrigues da Silva, Francisco Meirelles Bastos de Oliveira
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引用次数: 0

Abstract

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 γ-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.

bur1-107突变体延迟G1/S转变,减轻了检查点缺陷酵母的羟基脲敏感性。
在酿酒酵母中,周期蛋白依赖性激酶Bur1主要以其促进转录延伸的作用而闻名,从而调节基因表达。在这项研究中,我们研究了BUR1等位基因(BUR1 -107)与检查点激酶Mec1和Rad53的零突变体之间的遗传相互作用。值得注意的是,Bur1 -107减轻了mec1和rad53突变体对羟基脲(HU)的敏感性,这表明当检查点信号通路受损时,Bur1活性变得有害。此外,Bur1 -107突变延缓了g1到s的相变,这表明Bur1在细胞周期进程中起着关键作用。在hu处理的mec1突变体中,bur1-107减少了γ-H2A的积累,促进了s期的恢复,抑制了亚g1群体的形成。总之,这些发现表明bur1驱动的g1 - s期进展加剧了暴露于HU的检查点缺陷细胞的DNA损伤和细胞死亡。这项研究强调了Bur1在调节检查点受损细胞对复制应激的细胞反应中的新作用。
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来源期刊
Genetics
Genetics GENETICS & HEREDITY-
CiteScore
6.90
自引率
6.10%
发文量
177
审稿时长
1.5 months
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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