PDF(Pubmed)
Abstract：
Pre-mRNA splicing plays a key role in the regulation of gene expression. Recent discoveries suggest that defects in pre-mRNA splicing, resulting from the dysfunction of certain splicing factors, can impact the expression of genes crucial for genome surveillance mechanisms, including those involved in cellular response to DNA damage. In this study, we analyzed how cells with a non-functional spliceosome-associated Gpl1-Gih35-Wdr83 complex respond to DNA damage. Additionally, we investigated the role of this complex in regulating the splicing of factors involved in DNA damage repair. Our findings reveal that the deletion of any component within the Gpl1-Gih35-Wdr83 complex leads to a significant accumulation of unspliced pre-mRNAs of DNA repair factors. Consequently, mutant cells lacking this complex exhibit increased sensitivity to DNA-damaging agents. These results highlight the importance of the Gpl1-Gih35-Wdr83 complex in regulating the expression of DNA repair factors, thereby protecting the stability of the genome following DNA damage.
摘要：
前mRNA剪接在基因表达调控中起关键作用。最近的发现表明，前mRNA剪接的缺陷，由于某些剪接因子的功能障碍，可以影响对基因组监控机制至关重要的基因的表达，包括那些参与细胞对DNA损伤的反应。在这项研究中,我们分析了具有非功能性剪接体相关Gpl1-Gih35-Wdr83复合物的细胞对DNA损伤的反应.此外,我们研究了这种复合物在调节DNA损伤修复相关因子剪接中的作用。我们的发现表明，Gpl1-Gih35-Wdr83复合物中任何成分的缺失都会导致DNA修复因子未剪接的前mRNA的大量积累。因此,缺乏这种复合物的突变细胞对DNA损伤剂的敏感性增加。这些结果突出了Gpl1-Gih35-Wdr83复合物在调节DNA修复因子表达中的重要性，从而保护DNA损伤后基因组的稳定性。
