DNA损伤反应的下降,以及肌源性差异化
Haser H Sutcu1, Phoebe Rassinoux2, Lise-Marie Donnio2
1Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAcc, Fontenay-aux-Roses, France.
Life science alliance
|November 22, 2023
概括
肌肉细胞与分裂细胞不同,在辐射后的DNA修复速度较慢. 这是由于专门的肌肉纤维 (肌管) 中的DNA修复蛋白水平降低,影响它们修复DNA损伤的能力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 有机体拥有DNA损伤反应 (DDR) 机制来修复DNA损伤并维持细胞功能.
- 虽然复制细胞中的DDR已经得到了充分的研究,但转移后细胞的修复机制在很大程度上仍未知.
- 肌肉纤维,专门的转移后细胞,容易受到与年龄相关的退化和放射治疗损伤.
研究的目的:
- 为了研究和比较肌肉纤维的DNA修复能力与增殖性肌细胞.
- 分析基切除修复 (BER),非同类末端连接 (NHEJ) 和同类重组 (HR) 的效率,以应对电离辐射 (IR) 诱导的DNA损伤.
- 阐明肌肉纤维核和肌肉细胞之间的DNA修复动力学潜在差异的分子基础.
主要方法:
- 对差异化髓管 (转基因后) 和肌细胞 (增殖) 中的DNA修复机制的比较研究.
- 专注于DNA修复途径:基切除修复,非同类末端连接和同类重组.
- 评估蛋白质招募动力学对IR诱导的DNA损伤部位的评估,并测量稳定状态蛋白质水平.
主要成果:
- 与神经细胞相比,转移后的神经管显示出显著减弱的动力学来招募DNA修复蛋白到IR损坏的DNA部位.
- 在肌管中观察到关键蛋白质的稳定状态水平降低,这些蛋白质参与了基切除修复和同源重组.
- 这些发现表明,高度分化肌肉细胞的DNA修复能力受损.
结论:
- 肌肉纤维具有减少修复电离辐射诱导的DNA损伤的能力,特别是在高度分化状态 (肌管) 中.
- 肌管中BER和HR的效率降低与关键修复蛋白的水平降低有关.
- 这种受损的DNA修复可能会导致肌肉组织对与年龄相关的退化和放射治疗副作用的脆弱性.
相关概念视频
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Overview of DNA Repair
31.1K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.1K
Satellite Stem Cells and Muscular Dystrophy
2.0K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.0K
DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K


