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由RFA不足引起的基因组不稳定性和适应性进化在Saccharomyces cerevisiae中

Runbiao Zhang¹, Liyan Tian¹, Min He¹

¹Ocean College, Zhejiang University, Zhoushan 316021, China.

Current issues in molecular biology

|February 27, 2026

概括

复制因子A (RFA) 缺乏导致酵母严重的基因组不稳定,导致DNA损伤和突变. 细胞通过不激活DNA修复基因来适应,从而使细胞在压力下生存.

科学领域:

遗传学遗传学是一个
分子生物学分子生物学
基因组不稳定性基因组不稳定性

背景情况:

复制因子A (RFA) 对于DNA复制和修复至关重要.
低RFA剂量不足可能导致基因组不稳定.
了解RFA的作用是理解DNA复制应激反应的关键.

研究的目的:

为了研究由于RFA剂量不足而导致的Saccharomyces cerevisiae的基因组变化.
阐明RFA缺乏影响DNA完整性的机制.
探索细胞利用适应性策略来生存RFA诱导的复制压力.

主要方法:

促进体替代策略来控制RFA基因表达.
突变积累的实验. 突变积累的实验.
全基因组测序以识别突变.
APOBEC3B诱导的突变发生试验.
对DNA修复基因失活的分析.

主要成果:

转录抑制RFA2或RFA3会导致严重的生长缺陷.
缺少RFA导致单体性增加,终端缺失和异构性丧失.
暴露的单链DNA (ssDNA) 的积累偏向于滞后链.
不匹配修复 (MMR) 基因 (MSH2,PMS1) 的自发失活使得一个生存优势.
超突变表型允许部分生长恢复.

结论:

为了保持基因组完整性,RFA剂量至关重要.
复制应激会诱导特定的突变特征.
细胞调节DNA修复通路,就像MMR一样,作为对RFA不足的适应性反应.
这项研究揭示了RFA剂量,复制压力和适应性进化之间的联系.

关键词:

复制DNA复制DNA复制DNA复制DNA复制复制因子A 是一个复制因子.基因组稳定性的基因组稳定性不匹配的维修维修不匹配的维修复制压力是复制的压力.

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