Base excision repair of 8-oxoG in dinucleosomes.

Base excision repair of 8-oxoG in dinucleosomes.
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二核小体中8-oxog的碱基切除修复。

DOI:
10.1093/nar/gkr761
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发表时间:
2012-01
影响因子:
14.9
通讯作者:
Angelov D
Angelov D
中科院分区:
生物学2区
文献类型:
--
作者:
Menoni H;Shukla MS;Gerson V;Dimitrov S;Angelov D

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在这项工作中,我们研究了染色质结构对 8-oxoG 碱基切除修复 (BER) 效率的影响。作为模型系统,我们使用了与连接组蛋白 H1 组装的精确定位的双核小体。将单个 8-oxoG 插入双核小体模板内的接头或核心颗粒 DNA 中。我们发现,在组蛋白 H1 不存在的情况下,糖基化酶 OGG1 从接头 DNA 中去除 8-oxoG,并以与裸露 DNA 相同的效率切割 DNA。相比之下,组蛋白 H1 的存在导致接头 DNA 中 8-oxoG 启动修复的效率降低近 10 倍,与接头 DNA 长度无关。无论组蛋白 H1 存在或不存在,核小体 DNA 中 8-oxoG 的修复都会受到严重阻碍。分子伴侣诱导的 H1 摄取恢复了糖基化酶诱导的从接头 DNA 中去除 8-oxoG 的效率,但不能从核小体 DNA 中去除。然而,我们表明,组蛋白 H1 的去除和核小体重塑对于有效去除核小体 DNA 中的 8-oxoG 都是必要且充分的。最后,提出了染色质模板中 8-oxoG 的 BER 模型。
In this work we have studied the effect of chromatin structure on the base excision repair (BER) efficiency of 8-oxoG. As a model system we have used precisely positioned dinucleosomes assembled with linker histone H1. A single 8-oxoG was inserted either in the linker or the core particle DNA within the dinucleosomal template. We found that in the absence of histone H1 the glycosylase OGG1 removed 8-oxoG from the linker DNA and cleaved DNA with identical efficiency as in the naked DNA. In contrast, the presence of histone H1 resulted in close to 10-fold decrease in the efficiency of 8-oxoG initiation of repair in linker DNA independently of linker DNA length. The repair of 8-oxoG in nucleosomal DNA was very highly impeded in both absence and presence of histone H1. Chaperone-induced uptake of H1 restored the efficiency of the glycosylase induced removal of 8-oxoG from linker DNA, but not from the nucleosomal DNA. We show, however, that removal of histone H1 and nucleosome remodelling are both necessary and sufficient for an efficient removal of 8-oxoG in nucleosomal DNA. Finally, a model for BER of 8-oxoG in chromatin templates is suggested.
DOI: 10.1083/jcb.153.7.1341
发表时间: 2001-06-25
期刊: The Journal of cell biology
影响因子: --
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发表时间: 2004-07-01
期刊: EMBO REPORTS
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DOI: 10.1093/emboj/20.22.6383
发表时间: 2001-11-15
期刊: EMBO JOURNAL
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DOI: 10.1016/s0959-437x(97)80124-4
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影响因子: 4
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