ASS1在代谢上有助于核和细胞质p53介导的DNA损伤反应
Lisha Qiu Jin Lim1, Lital Adler1, Emma Hajaj1,2
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Nature metabolism
|June 10, 2024
概括
癌症中阿尔金酸合成酶 (ASS1) 的损失促进了DNA损伤和细胞周期的进展. 通过p53调节的ASS1有助于在DNA损伤后保持基因组稳定.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- 尿素循环酶氨酸酸合成酶 (ASS1) 的下调与各种瘤的预后不佳有关.
- 由于核酸失衡,ASS1损失可能导致代谢转变,有利于胺合成,增殖和突变发生.
研究的目的:
- 研究ASS1在结肠癌细胞和纤维细胞中对DNA损伤反应和细胞周期调节的作用.
- 阐明ASS1影响基因组稳定性和癌细胞适应性的机制.
主要方法:
- 分析ASS1表达及其对结肠癌细胞和纤维细胞具有和没有诱导的DNA损伤 (多克索鲁比) 的功能影响.
- 研究了p53在调节ASS1表达和功能的参与.
- 研究了ASS1和ASL在染色质重塑和基因转录中的核作用.
主要成果:
- 长时间的ASS1损失被发现会促进DNA损伤和细胞周期进展.
- 在DNA受损后,ASS1表达在细胞质和细胞核中增加,部分依赖p53.
- 细胞质ASS1通过限制核酸合成来抑制细胞循环;核ASS1和ASL产生烟酸,破坏SMARCC1-SNF5的稳定,并降低细胞循环基因的转录.
结论:
- ASS1作为p53网络的一个组成部分,暂停细胞循环的进展,以促进基因组维护和DNA损伤后的生存.
- 丢失ASS1有助于DNA损伤,并促进细胞循环的进展,可能增强癌细胞的适应性和突变发生.
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