Fanconi anemia : a disorder defective in the DNA damage response
Fanconi anemia : a disorder defective in the DNA damage response
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范可尼贫血：一种 DNA 损伤反应缺陷的疾病
DOI：
10.1007/s12185-011-0832-9
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发表时间：
2011
期刊：
影响因子：
2.1
通讯作者：
Takata M
中科院分区：
文献类型：
--
作者：
Kitao H;Takata M
我们体内除红细胞外的每个细胞都有基因组，其稳定性对生命至关重要。 DNA 在细胞增殖过程中精确复制，并且即使在终末分化后也能稳定维持，作为协调细胞新陈代谢的信息库。不幸的是，我们的世界充满了基因组稳定性的潜在威胁。 DNA 可能会自发降解，复制过程中可能会发生错误，或者代谢副产物（例如氧自由基或醛）可能会化学修饰其核苷酸碱基（即 DNA 加合物）。电离辐射、紫外线和化疗药物都是众所周知的 DNA 损伤的外源来源 [1, 2]。为了确保细胞健康，生物体开发了复杂的分子网络来检测和修复 DNA 损伤 [3]。如果DNA损伤的有害影响超过了细胞的修复能力，它就会在基因组中积累，导致细胞周期检查点的激活（为修复赢得时间）、细胞死亡（细胞凋亡或坏死），或者在检查点失败或细胞死亡的情况下，DNA损伤转化为突变。这可能导致细胞增殖不良、出现恶性肿瘤、干细胞维持受损或早发衰老 [1, 2]。由于所有细胞活动在某种程度上都依赖于基因组，因此控制基因组稳定性的机制在一般生物医学研究中至关重要。血细胞也不例外。
Every cell in our body other than red blood cells has a genome, the stability of which is crucial for life. The DNA is precisely replicated during cell proliferation, and is stably maintained, even after terminal differentiation, as a repository of information that orchestrates the cell’s metabolism. Unfortunately, our world is full of potential threats to genomic stability. DNA may degrade spontaneously, errors may occur during its replication, or metabolic byproducts, such as oxygen radicals or aldehydes, may chemically modify its nucleotide bases (ie DNA adducts). Ionizing radiation, ultraviolet light, and chemotherapeutic drugs are all well-known exogenous sources of DNA damage [1, 2].To ensure cellular fitness, organisms have developed an elaborate molecular network to detect and repair DNA damage [3]. If deleterious effects of DNA damage exceed the cell’s repair capacity, it accumulates in the genome, leading to activation of cell cycle checkpoints (buying time for repair), cell death (apoptosis or necrosis), or, in the failure of checkpoints or cell death, conversion of DNA damage to mutations. This may result in poor cell proliferation, emergence of malignancy, impaired stem cell maintenance, or early-onset aging [1, 2]. Since all cellular activity in a way relies on the genome, the mechanisms that govern genomic stability are fundamentally important in biomedical research in general. Blood cells are no exception.