The nucleosome-binding protein HMGN2 modulates global genome repair.

The nucleosome-binding protein HMGN2 modulates global genome repair.
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DOI:
10.1111/j.1742-4658.2009.07375.x
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发表时间:
2009-11
期刊:
The FEBS journal
影响因子:
--
通讯作者:
Bergel M
Bergel M
中科院分区:
其他
文献类型:
--
作者:
Subramanian M;Gonzalez RW;Patil H;Ueda T;Lim JH;Kraemer KH;Bustin M;Bergel M

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HMGN家族包括与核小体结合并改变染色质结构的核蛋白。在这里,我们报道了缺乏HMGN2或HMGN1a,或缺乏HMGN1a和HMGN2的DT40鸡细胞对紫外线照射的杀伤非常敏感。HMGN1a和HMGN2缺失或仅HMGN2缺失可增加紫外线诱导的G2-M检查点阻滞程度和细胞凋亡率。HMGN零突变细胞显示紫外线诱导的DNA损伤从天然染色质中去除较慢,但核苷酸切除修复保持完整,通过宿主细胞再激活试验测量。这些结果确定HMGN2是核苷酸切除修复途径的全球基因组修复亚途径的一个组成部分,并可能表明HMGN2促进DNA修复蛋白进入和修复紫外线诱导的染色质DNA损伤的能力。我们发现HMGNs在全球DNA修复中发挥作用,扩大了这些蛋白质在维持基因组完整性方面的作用。
The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here, we report that DT40 chicken cells lacking either HMGN2 or HMGN1a, or lacking both HMGN1a and HMGN2, are hypersensitive to killing by UV irradiation. Loss of both HMGN1a and HMGN2 or only HMGN2 increases the extent of UV-induced G2–M checkpoint arrest and the rate of apoptosis. HMGN null mutant cells showed slower removal of UV-induced DNA lesions from native chromatin, but the nucleotide excision repair remained intact, as measured by host cell reactivation assays. These results identify HMGN2 as a component of the global genome repair subpathway of the nucleotide excision repair pathway, and may indicate that HMGN2 facilitates the ability of the DNA repair proteins to access and repair UV-induced DNA lesions in chromatin. Our finding that HMGNs play a role in global DNA repair expands the role of these proteins in the maintenance of genome integrity.
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