Wdr70 regulates histone modification and genomic maintenance in fission yeast
Wdr70 regulates histone modification and genomic maintenance in fission yeast
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Wdr70 调节裂殖酵母中的组蛋白修饰和基因组维护
DOI：
10.1016/j.bbamcr.2020.118665
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发表时间：
2020
影响因子：
5.1
通讯作者：
Liu Cong
中科院分区：
文献类型：
--
作者：
Zeng Ming;Tang Zizhi;Guo Li;i;Wang Xiaojun;Liu Cong
真核基因组被包装成高度浓缩的染色质，这种抑制染色质的障碍可以通过组蛋白修饰酶改变染色质结构来克服。在这里，我们报道了裂殖酵母中的Wdr70(SpWdr70)在细胞周期进程、染色质结构和DNA修复等多个细胞过程中发挥重要作用。Wdr70基因缺失会导致细胞周期延迟、对DNA损伤试剂敏感和快速的表型变化。此外，我们还观察到Wdr70与调节检查点和同源重组(HR)的基因之间有很强的遗传交互作用，从而明确了Wdr70在DNA末端切除中的作用。最后，我们证明Wdr70的功能可以归因于DNA双链断裂(DSB)附近的组蛋白H_2B(UH_2B)的单素化。综上所述，我们的数据表明，Wdr70和H2B依赖于单泛素化的染色质调制是染色质动态平衡和遗传稳定性所必需的。
Eukaryotic genomes are packaged into highly condensed chromatin and this repressive chromatin barrier can be overcome by altering the chromatin structure via histone modification enzymes. Here, we reportWdr70inSchizosaccharomyces pombe(spWdr70) plays important roles in multiple cellular processes including cell cycle progression, chromatin structure and DNA repair. Depletion ofWdr70gene causes cell cycle delay, hypersensitivity to DNA damage reagents and quick phenotypic changes. Moreover, we observed strong genetic interaction betweenWdr70and genes regulating checkpoint and homologous recombination (HR), pinpointing the function ofWdr70to DNA end resection. Finally, we show that the function ofWdr70could be attributed to monoubiquitination of histone H2B (uH2B) in the vicinity of DNA double strand breaks (DSBs). Taken together, our data reveal that Wdr70 and H2B monoubiquitination-dependent chromatin modulation is required for chromatin homeostasis and genetic stability.