靶向i-Motif调控核酸中癌基因的表达

Prashansa Agrawal
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引用次数: 0

摘要

维持地球生命所需的基本分子包括碳水化合物、脂质、蛋白质和核酸(DNA和RNA)。DNA被认为是生命的基石,可以采用各种类型的二级结构。Gehring等人首次揭示具有较长胞嘧啶延伸的DNA序列可以形成称为i-Motifs的非常规二级结构[1]。这些i- motif是非常动态的插层四螺旋结构,已知存在于酸性条件下。这些胞嘧啶延伸并不是不规则地分布在整个基因组中,而是在基因组内的几个癌基因的启动子区域和染色体的末端区域端粒中富集。i-motif的形成和稳定可能在基因表达中起着至关重要的作用[2-4],例如,羧化单壁碳纳米管对人类端粒i-motif的稳定可以抑制端粒酶,从而导致端粒脱帽、DNA损伤反应和细胞凋亡[5]。
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Regulation of Oncogene Expression via Targeting i-Motif in Nucleic Acids
The basic molecules required for sustaining life on earth include carbohydrates, lipids, proteins, and nucleic acids (DNA and RNA). DNA is considered to be the building block of life and can adopt various types of secondary structures. Gehring et al. revealed for the first time that DNA sequences having long cytosine stretch can form unconventional secondary structures called i-Motifs [1]. These i-Motifs are very dynamic intercalated, quadruple-helical structures and known to exist under acidic conditions. These cytosine stretches are not erratically located throughout the genome but enriched in the promoter regions of several oncogenes within the genome and in telomeres, the terminal regions of chromosomes. The formation and stabilization of i-motif may play a crucial role in gene expression [2-4], such as, the stabilization of the human telomeric i-motif by carboxylated single-walled carbon nanotubes inhibit telomerase that leads to telomere uncapping, DNA damage response and apoptosis [5].
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