分相超增强剂在基因组DNA上赋予了先天的放射电阻
Koki Matsumoto1, Dini Kurnia Ikliptikawati2, Kei Makiyama1
1Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Journal of radiation research
|June 14, 2024
概括
由BRD4蛋白凝聚物形成的超级增强剂 (SE) 保护DNA免受辐射损伤,从而赋予癌细胞抗辐射能力. 破坏这些SE可能会提高放射治疗的有效性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 生物分子凝结物调节细胞内过程和病原性.
- BRD4蛋白为基因转录建立相分离的超级增强剂 (SE).
- SEs可能会通过辐射来限制水的电离,这表明潜在的抗辐射能力.
研究的目的:
- 调查SE是否会使癌细胞产生抗辐射能力.
- 探索BRD4相分离在DNA保护中的作用.
- 评估破坏SEs用于放射治疗的治疗潜力.
主要方法:
- 在体外使用芬顿反应激素进行DNA损伤测定.
- 同焦点成像分析SE焦点和DNA损伤焦点.
- 评估癌细胞的放射电阻,有或没有BRD4不稳定剂ARV-771.
主要成果:
- 当BRD4阶段与DNA分离时,DNA损伤显著减少.
- 在被辐射的细胞中,SE焦点和DNA损伤焦点相互排斥.
- 当辐射与BRD4破坏稳定剂ARV-771.1相结合时,癌细胞的抗辐射能力下降.
结论:
- 天生耐辐射的基因组区域是由癌细胞的相分离驱动的.
- 通过保护DNA,BRD4介导的SE赋予了抗辐射的能力.
- 破坏相隔组件可能会提高放射治疗的疗效.
更多相关视频
相关概念视频
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K


