REV3通过激活转化DNA合成和S内部检查点来促进细胞对5-氧氨的耐受性
Mubasshir Washif1, Ryotaro Kawasumi1, Kouji Hirota1
1Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan.
PLoS genetics
|July 2, 2024
概括
这项研究显示,REV3,一种参与DNA修复的蛋白质,对于细胞对化疗药物floxuridine (FUdR) 的耐受性至关重要. 缺乏REV3的细胞对FUdR的敏感性增加,突出了REV3在DNA损伤耐受性中的作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 弗洛克苏里丁 (FUdR) 是用于化疗的5-甲 (5-FU) 的活性代谢物.
- FUdR抑制了DNA复制和thymidylate合成酶,导致DNA损伤和细胞死亡.
- 细胞对FUdR耐受性的机制尚未完全理解.
研究的目的:
- 研究细胞对FUdR.R.抗性的机制.
- 使用突变查方法识别参与FUdR耐受性的基因.
主要方法:
- 在FUdR过敏性基因组维护系统中缺乏DT40突变的查.
- 在FUdR暴露后,对REV3缺乏细胞 (REV3-/-) 进行复制忠实性和细胞周期进展的分析.
- 研究DNA损伤检查点的激活,包括Chk1酸化和ATR通路的参与.
主要成果:
- REV3被确定为FUdR耐受性的关键因素.
- 缺乏REV3的细胞在FUdR受损的DNA模板上表现出受损的复制.
- REV3 缺乏导致S阶段细胞周期停止和Chk1酸化有缺陷.
- REV3与ATR-Chk1通路并行调解DNA检查点的激活.
结论:
- REV3在细胞对FUdR.的耐受性方面发挥着重要的,以前未被识别的作用.
- REV3的转化合成 (TLS) 功能对于在FUdR损坏的DNA上进行复制至关重要.
- REV3有助于DNA损伤检查点的激活,影响FUdR治疗期间的细胞存活率.
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