...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Molecular Biology >DNA double-strand break repair is impaired in presenescent Syrian hamster fibroblasts
【24h】

DNA double-strand break repair is impaired in presenescent Syrian hamster fibroblasts

机译：DNA双链断裂修复在衰老的叙利亚仓鼠成纤维细胞中受损

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Studies of DNA damage response are critical for the comprehensive understanding of age-related changes in cells, tissues and organisms. Syrian hamster cells halt proliferation and become presenescent after several passages in standard conditions of cultivation due to what is known as «culture stress». Using proliferating young and non-dividing presenescent cells in primary cultures of Syrian hamster fibroblasts, we defined their response to the action of radiomimetic drug bleomycin (BL) that induces DNA double-strand breaks (DSBs). The effect of the drug was estimated by immunoblotting and immunofluorescence microscopy using the antibody to phosphorylated histone H2AX (gH2AX), which is generally accepted as a DSB marker. At all stages of the cell cycle, both presenescent and young cells demonstrated variability of the number of gH2AX foci per nucleus. gH2AX focus induction was found to be independent from BL-hydrolase expression. Some differences in DSB repair process between BL-treated young and presenescent Syrian hamster cells were observed: (1) the kinetics of gH2AX focus loss in G0 fibroblasts of young culture was faster than in cells that prematurely stopped dividing; (2) presenescent cells were characterized by a slower recruitment of DSB repair proteins 53BP1, phospho-DNA-PK and phospho-ATM to gH2AX focal sites, while the rate of phosphorylated ATM/ATR substrate accumulation was the same as that in young cells. Our results demonstrate an impairment of DSB repair in prematurely aged Syrian hamster fibroblasts in comparison with young fibroblasts, suggesting age-related differences in response to BL therapy.
机译：DNA损伤反应的研究对于全面了解细胞，组织和生物体中与年龄相关的变化至关重要。由于所谓的“培养压力”，叙利亚仓鼠细胞在标准培养条件下传代数次后会停止增殖并进入衰老状态。我们在叙利亚仓鼠成纤维细胞的原代培养物中使用增殖的年轻且未分裂的衰老细胞，我们定义了它们对放射诱导药物博来霉素（BL）诱导DNA双链断裂（DSBs）作用的反应。使用抗磷酸化组蛋白H2AX（gH2AX）的抗体通过免疫印迹和免疫荧光显微镜术评估了药物的作用，该抗体通常被认为是DSB标记。在细胞周期的所有阶段，衰老细胞和年轻细胞均显示出每个细胞核中gH2AX灶的数量是可变的。发现gH2AX聚焦诱导独立于BL水解酶表达。在BL处理过的年轻和衰老的叙利亚仓鼠细胞之间，DSB修复过程存在一些差异：（1）年轻培养的G0成纤维细胞中gH2AX聚焦丢失的动力学比早已停止分裂的细胞快。 （2）衰老前期细胞的特征是DSB修复蛋白53BP1，磷酸DNA-PK和磷酸ATM较慢地募集到gH2AX焦点部位，而磷酸化ATM / ATR底物的积累速率与年轻细胞相同。我们的结果表明，与年轻的成纤维细胞相比，叙利亚老龄仓鼠成纤维细胞的DSB修复受到损害，表明对BL治疗的反应与年龄有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号