Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage
Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage
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DOI：
10.1016/j.bbrc.2010.11.094
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发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Ohnishi, Takeo
中科院分区：
文献类型：
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作者：
Noda, Taichi;Takahashi, Akihisa;Ohnishi, Takeo
本文描述的工作检查了范可尼贫血 (FA) 修复途径对甲醛引起的 DNA 损伤的作用。使用以下细胞类型：小鼠胚胎成纤维细胞系FANCA(-/-)、FANCC(-/-)、FANCA(-/-)C(-/-)、FANCD2(-/-)及其亲本细胞、中国仓鼠细胞系FANCD1突变体(mt)、FANCGmt、其回复细胞以及相应的野生型(wt)细胞。甲醛处理后通过集落形成测定确定细胞存活率。使用免疫细胞化学 γ H2AX 染色法检测 DNA 双链断裂 (DSB)。虽然FANCA(-/-)、FANCC(-/-)和FANCA(-/-)C(-/-)细胞对甲醛的敏感性与熟练细胞相当，但FANCD1mt、FANCGmt和FANCD2-/-细胞对甲醛比相应的熟练细胞更敏感。结果发现，同源重组（HR）修复是由甲醛诱导的。此外，FANCD1mt 细胞中的 γ H2AX 病灶比 FANCD1wt 细胞中持续的时间更长。这些发现表明，甲醛诱导的 DSB 由 HR 通过 FA 修复途径进行修复，该途径独立于 FA 核核心复合物。 (C) 2010 Elsevier Inc. 保留所有权利。
The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA(-/-), FANCC(-/-), FANCA(-/-)C(-/-), FANCD2(-/-) and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs)were detected with an immunocytochemical gamma H2AX-staining assay. Although the sensitivity of FANCA(-/-), FANCC(-/-) and FANCA(-/-)C(-/-) cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2-/- cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, gamma H2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. (C) 2010 Elsevier Inc. All rights reserved.