中文摘要：

c-Myc是一种泛在性的转录因子,它调控着许多涉及细胞增殖、分化、凋亡等生命活动的基因.实验结果表明在骨肉瘤细胞U2OS中过表达c-Myc和Nbs1都能减弱阿霉素降低集落形成的能力.进一步的实验证实c-Myc的这种作用与Nbs1有关,Nbs1是c-Myc的靶基因.染色质免疫沉淀实验显示,c-Myc招募组蛋白乙酰化酶p300复合物到Nbs1启动子区,引起了组蛋白H4的乙酰化,定位在Nbs1启动子区的相邻的两个E-box对c-Myc的结合是必要的.上述结果说明c-Myc减弱阿霉素的作用部分是通过调控Nbs1来实现的.这也提示了c-Myc在阿霉素诱导的DNA损伤修复中起作用。

英文摘要：

c-Myc is a ubiquitous transcription factor that regulates a wide variety of genes involved in the control of cell proliferation,differentiation and apoptosis.It was demonstrated that over-expressions of c-Myc and Nbs1 attenuated the ability of doxorubicin in reduction of colony formation in U2OS cells,and it was found that this effect of c-Myc was associated with Nbs1.It can be confirmed that Nbs1 is a target gene of c-Myc.Chromatin immunoprecipitation assays reveal that c-Myc recruited the histone acetyltransferase p300 complex to the promoter region of Nbs1 gene,resulting in an increased level of acetylated histone H4.Furthermore,it was found that the two proximal E-box elements located in Nbs1 promoter region were essential for the c-Myc binding.Thus,it was concluded that c-Myc attenuates the effect of doxorubicin partially through regulating Nbs1,implicating its roles in repair of DNA breakage induced by doxorubicin.