Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin
Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin
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DOI：
10.1093/emboj/cdg142
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发表时间：
2003-04-01
期刊：
影响因子：
11.4
通讯作者：
Bustin, M
中科院分区：
文献类型：
--
作者：
Birger, Y;West, KL;Bustin, M
我们报告说，HMGN 1，核小体结合蛋白，不稳定的高阶染色质结构，调节修复率的紫外线（UV）诱导的DNA损伤染色质。Hmgn 1（-/-）小鼠胚胎成纤维细胞（MEFs）对紫外线高度敏感，与Hmgn 1（+/+）MEFs相比，Hmgn 1（-/-）MEFs染色质中光产物的去除率降低;然而，宿主细胞再活化试验和DNA阵列分析表明，Hmgn 1（-/-）MEFs中的核苷酸切除修复（NER）途径保持完整。用表达野生型HMGN 1蛋白的质粒转染可以挽救HMGN 1（-/-）MEFs的UV超敏性，但不能用表达不结合核小体或不展开染色质的HMGN 1突变体的质粒转染。转录活性基因是小鼠NER途径的主要靶点，含有HMGN 1蛋白，HMGN 1蛋白的缺失降低了转录基因对核酸酶的可及性。通过减少高级染色质结构的压缩，HMGN 1促进了对UV损伤的DNA位点的访问，并提高了染色质中DNA修复的速率。
We report that HMGN1, a nucleosome binding protein that destabilizes the higher-order chromatin structure, modulates the repair rate of ultraviolet light (UV)-induced DNA lesions in chromatin. Hmgn1(-/-) mouse embryonic fibroblasts (MEFs) are hypersensitive to UV, and the removal rate of photoproducts from the chromatin of Hmgn1(-/-) MEFs is decreased as compared with the chromatin of Hmgn1(+/+) MEFs; yet, host cell reactivation assays and DNA array analysis indicate that the nucleotide excision repair (NER) pathway in the Hmgn1(-/-) MEFs remains intact. The UV hypersensitivity of Hmgn1(-/-) MEFs could be rescued by transfection with plasmids expressing wild-type HMGN1 protein, but not with plasmids expressing HMGN1 mutants that do not bind to nucleosomes or do not unfold chromatin. Transcriptionally active genes, the main target of the NER pathways in mice, contain HMGN1 protein, and loss of HMGN1 protein reduces the accessibility of transcribed genes to nucleases. By reducing the compaction of the higher-order chromatin structure, HMGN1 facilitates access to UV-damaged DNA sites and enhances the rate of DNA repair in chromatin.