转载聚合酶和DNA-蛋白质交联修复塑造了细胞对甲诱导的DNA损伤在ssDNA中的细胞反应
Thomas Blouin1, Elizabeth Ampolini1, Kristina Stayer1
1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, United States.
Nucleic acids research
|September 18, 2025
概括
甲 (FA) 导致DNA损伤,特别是在瓜中. 包括转化合成 (TLS) 和DNA-蛋白质交叉链路 (DPC) 修复在内的DNA修复途径协调,以防止因FA暴露而导致的突变和基因组不稳定性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 毒理学 毒理学 毒理学
背景情况:
- 甲 (FA) 是一种与癌症相关的反应性化物,形成像DNA-蛋白质交叉链接 (DPC) 这样的DNA添加物.
- 转移合成 (TLS) 聚合酶绕过持久的DNA损伤,有助于FA突变谱.
- 在绕过FA损坏时,DPC修复和TLS之间的相互作用仍然不清楚.
研究的目的:
- 调查DPC修复和TLS如何协调绕过FA诱导的DNA损伤.
- 确定不同TLS聚合酶如何影响FA突变谱.
- 阐明FA诱导的突变和基因组不稳定性背后的机制.
主要方法:
- 利用酵母突变记者系统研究FA诱导的DNA损伤.
- 评估了TLS和DPC修复在预防染色体不稳定和重排的作用.
- 研究了特定TLS聚合酶 (Rev1和Pol η) 在FA突变发生中的功能.
主要成果:
- 已确认的FA在单链DNA (ssDNA) 中优先致死氨酸残留物.
- 证明功能性TLS在FA暴露后可以防止染色体不稳定.
- 表明FA诱导的染色体重排取决于DPC修复.
- 确定TLS聚合酶Rev1和Pol η合作防止FA的突变发生.
结论:
- TLS和DPC修复通路对于协调FA诱导的ssDNA损伤的绕道至关重要.
- 通过TLS和DPC修复的协调作用,可以防止FA诱导的突变和染色体不稳定.
- Rev1 和 Pol η 在防止 FA 突变发生过程中发挥着关键作用,突出显示了 TLS 聚合酶功能的特异性.
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