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Substitution of Cytosine with Guanylurea Decreases the Stability of i-Motif DNA
Biochemistry ( IF 2.9 ) Pub Date : 2017-08-30 00:00:00 , DOI: 10.1021/acs.biochem.7b00628
Elisé P. Wright 1 , Katarzyna Lamparska 2 , Steven S. Smith 2 , Zoë A. E. Waller 1, 3
Affiliation  

Both 5-aza-2′-deoxycytidine (decitabine) and its primary breakdown product, 2′-deoxyriboguanylurea (GuaUre-dR), have been shown to act as mutagens and epimutagens that cause replication stress and alter both DNA methylation and gene expression patterns. As cytosine analogues, both are expected to be preferentially incorporated into regions of GC skew where runs of cytosine residues are sequestered on one strand and guanine residues on the other. Given that such regions have been identified as sites with the potential for effects on gene expression and replication stress linked to formation of alternative DNA secondary structures, it is of interest to determine the influence that these base analogues might have on the stability of structures of this kind. Here we report that incorporation of GuaUre-dR into an i-motif-forming sequence decreases both the thermal and pH stability of an i-motif despite the apparent ability of GuaUre-dR to base pair with cytosine.

中文翻译:

用鸟苷尿素取代胞嘧啶会降低i-Motif DNA的稳定性

5-氮杂2'-脱氧胞苷(地他滨)及其主要分解产物2'-脱氧核糖鸟嘌呤(GuaUre-dR)已被证明可作为诱变剂和表突变体,引起复制压力并改变DNA甲基化和基因表达模式。作为胞嘧啶类似物,预计两者都将优先掺入GC偏斜区域,在该区域中,胞嘧啶残基的运行被隔离在一条链上,而鸟嘌呤残基的隔离在另一条链上。鉴于已将此类区域确定为可能对基因表达和复制压力产生影响的位点,这些位点与形成替代性DNA二级结构有关,因此有兴趣确定这些碱基类似物可能对该结构的稳定性产生的影响种类。
更新日期:2017-08-30
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