增加MSH2和MSH3的表达会干扰DNA的新陈代谢 in vivo
Melisa Medina-Rivera1, Samantha Phelps1, Madhumita Sridharan2
1Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo NY, 14203, USA.
Nucleic acids research
|November 6, 2023
概括
高水平的Msh2-Msh3不匹配修复 (MMR) 复合物会破坏酵母中的DNA复制和修复. 这种过多的MMR蛋白质通过一种需要其ATPase活性的活性机制导致基因组不稳定.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 在Saccharomyces cerevisiae中,Msh2-Msh3不匹配修复 (MMR) 复合体在基因组稳定性中起着双重作用.
- 它修复插入/删除循环 (IDL) 并与各种DNA结构相互作用,影响同源重组和DNA损伤反应.
- 然而,Msh2-Msh3也可以促进基因组的不稳定性,特别是通过三核酸重复 (TNR) 扩张.
研究的目的:
- 研究Msh2-Msh3水平升高对DNA复制和修复的体内影响.
- 阐明Msh2-Msh3介导的基因组不稳定性背后的机制细节.
- 确定Msh2-Msh3在这些过程中的丰度和活性.
主要方法:
- 在Saccharomyces cerevisiae体内研究评估DNA复制和基切除修复.
- 对细胞循环停止表型的分析,包括对RAD9和ELG1的依赖,以及PCNA修饰.
- 调查对Msh2-Msh3 ATPase活性和下游MMR蛋白质的要求.
主要成果:
- 升高的Msh2-Msh3水平会干扰DNA复制和基切割修复 in vivo.
- 增加的Msh2-Msh3诱导了依赖RAD9和ELG1的细胞循环停止,并导致PCNA修饰.
- 这些效应取决于Msh2-Msh3 ATPase活性和下游MMR蛋白质,表明有一个活跃的破坏机制.
结论:
- 过量的Msh2-Msh3积极破坏DNA复制和修复途径.
- Msh2-Msh3蛋白质的丰富性是Msh2-Msh3介导的基因组不稳定性的关键因素.
- 这项研究为MMR复杂水平如何影响基因组稳定性提供了新的机制性见解.
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