DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation
DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation
复制标题
DNA损伤通过转录激活诱导N-乙酰转移酶NAT10基因表达
DOI：
10.1007/s11010-006-9390-5
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发表时间：
2007-06-01
影响因子：
4.3
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Liu, Haijing;Ling, Yun;Zhang, Bo
NAT 10（N-acetyltransferase 10）是一种具有组蛋白乙酰化活性的蛋白质，主要参与端粒酶活性的调节。目前的研究表明，它的转录激活的遗传毒性剂和可能的作用，DNA损伤。过氧化氢（H2 O2）和顺铂均能诱导NAT 10 mRNA表达增加，且呈剂量和时间依赖性。免疫荧光染色显示，H2 O2和顺铂均能诱导NAT 10蛋白在细胞核内聚集。H_2O_2和顺铂均能通过上游-615 ~+110 bp的序列激活NAT 10启动子的转录活性，并与核蛋白相互作用。NAT 10的异位表达可增加H2 O2或顺铂存在下的存活细胞数。上述结果提示，NAT 10可能参与DNA损伤反应，增强细胞对遗传毒性的抵抗力。
NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and primarily identified to be involved in regulation of telomerase activity. The presented research shows its transcriptional activation by genotoxic agents and possible role in DNA damage. NAT10 mRNA could be markedly increased by using hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the immunofluorescent staining revealed that the treatment of H2O2 or cisplatin induced focal accumulation of NAT10 protein in cellular nuclei. Both H2O2 and cisplatin could stimulate the transcriptional activity of the NAT10 promoter through the upstream sequences from -615 bp to +110 bp, with which some nuclear proteins interacted. Ectopic expression of NAT10 could enhance the number of survival cells in the presence of H2O2 or cisplatin. The above results suggested that NAT10 could be involved in DNA damage response and increased cellular resistance to genotoxicity.