Fission yeast Cds1 is responsible for the replication checkpoint activation and helps to protect replication fork collapse in response to hydroxyurea (HU). Here, we investigated the role of histone deacetylase in response to replication fork arrest and observed that in the presence of HU, the survival of cds1Δ cells was improved when the cells were simultaneously treated with histone deacetylase inhibitors. Furthermore, a mutation in the histone deacetylase gene, clr6, also suppresses the growth defect of cds1Δ cells in response to HU indicating a suppressive role of clr6-1 mutation in cds1 deletion background upon HU treatment. Interestingly, in response to HU, phosphorylation of Chk1 kinase and the number of Rad52YFP foci was reduced in cds1Δ clr6-1 double mutant as compared to cds1Δ single mutant indicating a decrease in the level of DNA damage in response to HU. Accordingly, the single-cell gel electrophoresis assay revealed a drastic reduction in the tail length of cds1Δ clr6-1 double mutant as compared to cds1Δ cells in the presence of HU suggesting the suppression of chromosomal defects in the double mutant. Taken together, we proposed that there could be transient suppression of fork collapse in cds1Δ clr6-1 double mutant upon HU treatment due to the delay in mitotic progression that leads to the facilitation of cell growth.

中文翻译：

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组蛋白脱乙酰基酶clr6中的突变可促进响应羟基脲的粟酒裂殖酵母cds1无效突变体的存活。

裂变酵母Cds1负责复制检查点的激活，并有助于保护复制叉因羟基脲（HU）而倒塌。在这里，我们研究了组蛋白脱乙酰基酶对复制叉停滞反应的作用，并观察到在HU的存在下，当同时用组蛋白脱乙酰基酶抑制剂处理细胞时，cds1Δ细胞的存活率得到了改善。此外，组蛋白脱乙酰基酶基因clr6的突变也抑制了响应于HU的cds1Δ细胞的生长缺陷，表明在HU处理后clr6-1突变在cds1缺失背景中具有抑制作用。有趣的是，为了回应HU，与cds1Δ单突变体相比，cds1Δclr6-1双突变体中Chk1激酶的磷酸化和Rad52YFP灶的数量减少，表明响应HU的DNA损伤水平降低。因此，单细胞凝胶电泳分析显示，与存在HU的cds1Δ细胞相比，cds1Δclr6-1双重突变体的尾巴长度显着减少，表明该双重突变体的染色体缺陷得到抑制。综上所述，我们提出，由于有丝分裂进程的延迟导致细胞生长的促进，在HU处理后cds1Δclr6-1双重突变体可能会暂时抑制前叉塌陷。单细胞凝胶电泳分析显示，与存在HU的cds1Δ细胞相比，cds1Δclr6-1双重突变体的尾巴长度显着减少，表明该双重突变体中的染色体缺陷得到抑制。综上所述，我们提出，由于有丝分裂进程的延迟导致细胞生长的促进，在HU处理后cds1Δclr6-1双重突变体中可能会暂时抑制前叉塌陷。单细胞凝胶电泳分析显示，与HU存在下的cds1Δ细胞相比，cds1Δclr6-1双重突变体的尾巴长度显着减少，表明该双重突变体的染色体缺陷得到抑制。综上所述，我们提出，由于有丝分裂进程的延迟导致细胞生长的促进，在HU处理后cds1Δclr6-1双重突变体中可能会暂时抑制前叉塌陷。