Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription, as shown in yeast and human cells, but the underlying mechanism and whether this link is universal is still unclear. To obtain further insight into the putative role of the THSC/TREX-2 complex in genome integrity, we have used Caenorhabditis elegans mutants of the thp-1 and dss-1 components of THSC/TREX-2. These mutants show similar defective meiosis, DNA damage accumulation and activation of the DNA damage checkpoint. However, they differ from each other regarding replication defects, as determined by measuring dUTP incorporation in the germline. Interestingly, this specific thp-1 mutant phenotype can be partially rescued by overexpression of RNase H. Furthermore, both mutants show a mild increase in phosphorylation of histone H3 at Ser10 (H3S10P), a mark previously shown to be linked to DNA-RNA hybrid-mediated genome instability. These data support the view that both THSC/TREX-2 factors prevent transcription-associated DNA damage derived from DNA-RNA hybrid accumulation by separate means.

中文翻译：

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THSC/TREX-2 缺陷会导致秀丽隐杆线虫复制应激和基因组不稳定。

转录是DNA代谢的重要过程，但它使DNA更容易受到DNA损伤。THSC/TREX-2 是一种保守的真核蛋白复合物，在 mRNP 生物发生和成熟中发挥关键作用，可防止基因组不稳定。这种不稳定性的一个来源与转录有关，如酵母和人类细胞中所示，但其潜在机制以及这种联系是否具有普遍性仍不清楚。为了进一步了解 THSC/TREX-2 复合物在基因组完整性中的假定作用，我们使用了 THSC/TREX-2 的 thp-1 和 dss-1 组件的秀丽隐杆线虫突变体。这些突变体表现出类似的减数分裂缺陷、DNA损伤积累和DNA损伤检查点激活。然而，它们在复制缺陷方面彼此不同，这是通过测量种系中 dUTP 的掺入来确定的。有趣的是，这种特定的 thp-1 突变体表型可以通过 RNase H 的过表达来部分挽救。此外，两种突变体都显示出组蛋白 H3 Ser10 (H3S10P) 磷酸化的轻微增加，该标记先前显示与 DNA-RNA 杂合体有关-介导的基因组不稳定性。这些数据支持这样的观点，即 THSC/TREX-2 因子通过不同的方式防止 DNA-RNA 杂合积累产生的转录相关 DNA 损伤。