核 porcupine 在DNA损伤反应中调解XRCC6/Ku70 S-palmitoylation
Yang Chen1,2, Mingming Xiao1,3, Yaqi Mo4
1Department of Biochemistry and Molecular Biology, The Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Experimental hematology & oncology
|November 4, 2024
概括
猪 (PORCN) 对于DNA损伤反应 (DDR) 至关重要,特别是在DNA修复中. 核PORCN调解Ku70棕化,这对于高效的DNA修复和辐射暴露后细胞存活至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- DNA损伤反应 (DDR) 依赖于蛋白质翻译后修饰 (PTM) 来预防遗传不稳定性和癌症.
- 棕化,一种保存的PTM,在癌症中经常失调,但其在DDR中的作用尚不清楚.
研究的目的:
- 研究 (PORCN) 在DNA损伤反应 (DDR) 中的作用.
- 阐明 PORCN 影响 DNA 修复通路的机制.
主要方法:
- 在CRISPR-Cas9基因编辑中创建PORCN淘汰细胞系.
- 对DNA修复 (同类重组/非同类末端结合),细胞活力,放射敏感性和蛋白质相互作用的测试.
- 质谱和棕化试验用于识别分子标和机制.
主要成果:
- 对于DDR来说,PORCN是至关重要的,PORCN缺乏会损害非同类末端连接 (NHEJ) 并增加辐射敏感性.
- 一个PORCN (nPORCN) 的核部分表现出S-转移酶活性,对于NHEJ激活至关重要.
- 在对电离辐射的反应中,nPORCN调解了XRCC6/Ku70在特定的囊残留物中的S-棕化.
- 为了形成DNA-PKcs/Ku70/Ku80复合体,需要依赖nPORCN的Ku70棕化.
结论:
- 核PORCN依赖Ku70 S-palmitoylation是DNA损伤反应的一个关键组成部分.
- 这种机制凸显了棕化在DNA修复和癌症生物学中的新作用.
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