持续的染色质变化和基因表达重编程在质母细胞瘤中随着广泛的DNA损伤而出现
Aram S Modrek1,2,3, Ken Chandradoss4,5,6, Catherine Do7,8
1Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA, 90033.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
广泛的DNA损伤会导致细胞中持久的遗传和非遗传变化,在修复后很长时间改变基因表达和基因组结构. 这些修改会影响细胞功能,可能会影响瘤的进展和对治疗的抗性.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- DNA 损伤可以改变基因调节的突变.
- 对染色质,基因表达和DNA修饰的长期影响尚不清楚.
- 目前的DNA修复范式集中在序列恢复上.
研究的目的:
- 在同时发生的DNA双链断裂 (DSB) 后,研究长期的遗传和非遗传变化.
- 分析染色体配置的变化,基因表达和DSBs后的结构变异.
主要方法:
- 在人类质母细胞瘤细胞中诱导许多Cas9介导的DSB.
- 在两周内追踪遗传和非遗传变异.
- 对基因组改变,TAD内部相互作用,基因表达和结构变异的分析.
主要成果:
- 检测到持续两个星期的兆基基基因基因组变化.
- 观察到从短暂转变为持久的远程cis和trans接触.
- 鉴定了基因表达的改变和相关的大型结构变异.
结论:
- 广泛的DNA损伤会导致持久的遗传和非遗传修饰.
- 这些修改改变了细胞功能,可能会影响瘤的结果.
- 研究结果表明,它在瘤进展和耐药细胞的出现中起着作用.
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