Influences of histone deacetylase inhibitors and resveratrol on DNA repair and chromatin compaction.
Influences of histone deacetylase inhibitors and resveratrol on DNA repair and chromatin compaction.
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组蛋白脱乙酰酶抑制剂和白藜芦醇对 DNA 修复和染色质压缩的影响
DOI：
10.1093/mutage/get034
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发表时间：
2013
期刊：
影响因子：
2.7
通讯作者：
PaulyK
中科院分区：
文献类型：
--
作者：
Keuser;Khobta;Gallé;Anderhub;Schulz;PaulyK
DNA的可及性是DNA损伤和修复的先决条件。因此，预计染色质结构对这两个过程都有重大影响，对基因组的稳定性有相反的影响。为了分析染色质致密化对各种类型的DNA修饰的产生和修复的影响，我们通过用组蛋白脱乙酰酶抑制剂或白藜芦醇处理来调节AS 52中国仓鼠卵巢细胞和HeLa细胞的整体染色质结构，并测量（i）由紫外线B诱导的嘧啶二聚体，（ii）氧化嘌呤产生的光敏化和（iii）单链断裂诱导过氧化氢，使用碱性洗脱技术。在用曲马斯他汀A或丁酸盐处理后，染色质致密化的降低（检测为DNA对DNA酶I的可接近性降低）略微增加了损伤的产生，但对整体修复率没有显著影响。与此相反，AS 52细胞与白藜芦醇的浓度，导致显着的染色质压实，只有适度的影响细胞增殖的孵育引起的所有三种类型的DNA修饰的修复率的强烈下降。在HeLa细胞中观察到类似但不太明显的效果。白藜芦醇对修复率的影响没有被沉默调节蛋白抑制剂EX-527或细胞内巯基水平的增加所拮抗。
Accessibility of DNA is a prerequisite for both DNA damage and repair. Therefore, the chromatin structure is expected to have major impact on both processes, with opposite consequences for the stability of the genome. To analyse the influence of chromatin compaction on the generation and repair of various types of DNA modifications, we modulated the global chromatin structure of AS52 Chinese hamster ovary cells and HeLa cells by treatment with either histone deacetylase inhibitors or resveratrol and measured the repair kinetics of (i) pyrimidine dimers induced by ultraviolet B, (ii) oxidised purines generated by photosensitisation and (iii) single-strand breaks induced by H2O2, using an alkaline elution technique. The decrease of chromatin compaction (detected as reduced DNA accessibility to DNase I) after treatment with trichostatin A or butyrate slightly increased the damage generation but had no significant effect on the global repair rates. In contrast, incubation of AS52 cells with resveratrol at concentrations that caused significant chromatin compaction and that had only moderate influence on cell proliferation gave rise to a strong decrease of the repair rates of all three types of DNA modifications. Similar, but less pronounced effects were observed in HeLa cells. The effects of resveratrol on the repair rates were not antagonised by the sirtuin inhibitor EX-527 or by an increase of the intracellular thiol levels.
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DOI：
10.18632/aging.100542
发表时间：
2013-03
期刊：
Aging
影响因子：
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作者：
Lakshminarasimhan M;Rauh D;Schutkowski M;Steegborn C
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DOI：
--
发表时间：
1989
期刊：
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