在布莱米辛治疗后,DNA损伤诱导的细胞内基因组变异
Marco Paolo Jacinto1, Stephen D Fried1,2, Marc M Greenberg1
1Department of Chemistry, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, United States.
Journal of the American Chemical Society
|April 25, 2022
概括
当基因组与基底部位发生反应时,会产生一种称为KMP的新基因组修饰. 这种非酶性修饰,KMP,影响DNA损伤后的细胞过程.
科学领域:
- 生物化学
- 分子生物学
- 遗传学
背景情况:
- 由于修复酶失活和病变恶化,对DNA损伤的评估是复杂的.
- 基因组溶酶与C4'-氧化基基位 (C4-AP) 反应,形成KMP并导致DNA链断裂.
研究的目的:
- 开发和应用一种用于识别细胞中的KMP修饰的化学蛋白质方法.
- 研究KMP作为DNA损伤诱导的基因组修饰的形成和流行情况.
主要方法:
- 开发一种用于检测KMP的化学蛋白质策略.
- 使用液体染色学-双重质谱法 (LC-MS/MS) 来识别HeLa细胞中的KMP.
主要成果:
- 每个细胞分别发现了超过6万个KMP修饰的基因组.
- 在核心基因组中的57个 lysine 残留物中,KMP 已被检测到.
- KMP是一种由DNA损伤引起的新型非酶基因组转化后修饰.
结论:
- KMP的形成代表了对DNA损伤的显著的非酶反应.
- 发现KMP可能会对细胞产生下游影响.
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