从细胞间DNA损伤差异预测关键的生物过程,通过基于模型的拟合
Kensuke Otsuka1, Kouki Uchinomiya1, Yuki Yaguchi2
1Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry, 1646 Abiko, Abiko-shi, Chiba 270-1194, Japan.
iScience
|December 25, 2024
概括
来自DNA双链断裂 (DSB) 的基因组应激会影响细胞生存和竞争性相互作用. 该Acta2基因调解这些相互作用,影响癌症微环境的进展和癌症风险评估.
科学领域:
- 细胞生物学 细胞生物学
- 基因组学就是基因组学.
- 数学建模的数学建模
背景情况:
- DNA双链断裂 (DSBs) 极大地影响了哺乳动物细胞的生存.
- 细胞修复能力决定了DSB对生存的影响.
- 基因组不稳定是癌症发展的标志.
研究的目的:
- 在特定序列的DSB负担下开发纤维细胞存活率的数学模型.
- 在混合培养中研究细胞对细胞相互作用,具有不同的DSB水平.
- 识别介导不同基因压力水平的细胞之间的竞争性相互作用的遗传因素.
主要方法:
- 使用限制酶 AsiSI.SI 诱导特定序列的 DSB.
- 使用Lotka-Volterra竞争方程分析细胞生长动态的数学建模.
- 在单一培养与混合培养中对细胞生长的比较分析.
主要成果:
- 诱导DSB的纤维细胞存活率被准确地建模.
- 混合培养中的细胞生长与零星的DSB负担符合竞争方程,表明修改因素.
- 鉴定出Acta2基因是具有不同DSB负荷的细胞之间的竞争性相互作用的关键调解者.
结论:
- 基因组应激,特别是DSBs,影响细胞健康和竞争相互作用.
- 阿克塔2基因在调解这些相互作用方面发挥着重要作用,可能驱动与癌症相关的纤维细胞表型.
- 这些发现表明,基因组压力是癌症微环境进展的决定因素,并为癌症风险估计提供了见解.
相关概念视频
Overview of DNA Repair
7.4K
7.4K
DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
Fixing Double-strand Breaks
11.8K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
11.8K
Base-pairing and DNA Repair
64.4K
64.4K
DNA Damage Can Stall the Cell Cycle
2.5K
2.5K


