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The up-regulated expression of hALP gene by genotoxic agents confers cellular resistance to DNA damage
Liu Haijing 1 #,Ling Yun 1,Lin Hou 2,Zhang Bo 2
1.Department of Pathology, Health Science Center of Peking University
2.Department of Pathology- Health Science Center of Peking University
*Correspondence author
#Submitted by
Funding: 教育部博士点基金(No.20040001147)
Opened online:17 March 2006
Accepted by: none
Citation: Liu Haijing ,Ling Yun,Lin Hou.The up-regulated expression of hALP gene by genotoxic agents confers cellular resistance to DNA damage[OL]. [17 March 2006] http://en.paper.edu.cn/en_releasepaper/content/5764
Objective: To confirm the response of hALP, a telomerase regulation-associated gene, to DNA damage. Methods: HeLa and Hep2 cells were respectively treated by genotoxic agents of hydrogen peroxide (H2O2) or cisplatin. The induced expression of hALP was measured by semi-quantitative RT-PCR and immunofluorescence. The transcriptional activity of hALP promoter was estimated by luciferase reporter assay. The cell survivor in the presence of genotoxic agents was analyzed by MTT method. Results: The level of hALP mRNA could be increased when treated by 0.2 ~ 1.6 mmol/L H2O2 and reach a peak in the concentration of 0.4 mmol/L. The induction could be observed after 6 h at the presence of 0.4 mmol/L H2O2 and hold high level for 36 h. Similarly, cisplatin induced hALP mRNA expression both in dose- or time-dependent. hALP protein was increased in immunofluorescent staining and concentrated in cellular nuclei with the treatment of H2O2 or cisplatin, which also stimulated the transcriptional activity of hALP promoter in luciferase assays through its upstream -705 ~ +20 nt region. On the other hand, HeLa cells expressing sense hALP gene could grow continuously in the present of 0.4 mmol/L H2O2 or 0.5µmol/L cisplatin, while cells with anti-sense hALP or control cells were slow in growth. Conclusions: The expression of hALP gene could be up-regulated by DNA damage through activating transcription of its promoter, and increase cellular resistance to genotoxic agents.
Keywords: DNA damage; Histone acetyltransferase; Telomerase; Gene expression

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