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首页> 外文期刊>Biochemistry >15-mer DNA duplexes containing an abasic site are thermodynamicallymore stable with adjacent purines than with pyrimidines
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15-mer DNA duplexes containing an abasic site are thermodynamicallymore stable with adjacent purines than with pyrimidines

机译：15-MEL DNA双链体，含有脱脂部位是热力学摩尔稳定的邻近嘌呤，而不是嘧啶

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摘要

Abasic site (AP)-containing duplexes, with flanking adenine (A) or cytosine (C) bases, were shown to be more stable with flanling A than vAth ~ bases S~gi, ~., XXartg,, W, axx~ ~iwgex, W ~999~ Chem. Res. Toxicol. 12, 917—923]. We investigated whether the lower-magnitude destabilization by an AP site, with A neighbors, is a general effect of the purine versus the pyrimidine neighbors. Duplex stability, as compared to that of the corresponding control duplexes, was markedly decreased by the incorporation of the AP site (x) opposite any of the four bases. However, for the duplexes containing T, A, or C opposite the AP site, replacement of the symmetric doublet flanking pyrimidine bases with purines resulted in a smaller destabilization effect. The average stabilizing effect of the symmetric doublet purine neighbors of an AP site opposite T, A, or C bases was 3.2 0C (ATm) and 1.3 kcab’mol (AAG037) compared to those of pyrimidine neighbors. In contrast, a GAP pair reduced or eliminated the differential effect of the neighbors. Using unrestrained molecular dynamics, it was shown that for the duplexes containing T opposite the AP site, with doublet pyrimidine neighbors, there was a larger magnitude of curvature around the lesion site than for the duplexes with the purines flanking the AP site. Purines flanking the AP site tend to shift toward each other, creating overlap, in contrast to the flanking pyrimidines. This indicates the possibility of stacking between purine bases at the AP site and can be the reason for the observed smaller thermodynamic destabilization of the duplexes with the AAxAA and GGxGG central sequences, as compared to those with TTxTT and CCxCC sequences. This work showed that for an AP site the GC content is not the only determinant of duplex stability, but rather is influenced more by whether purines or pyrimidines flank the AP site.
机译：Abasic位点（AP） - 毛细管（A）或胞嘧啶（C）碱的含有双链体，显示出比Vath〜碱〜Gi，〜。，Xxartg，W，AXX〜 〜iwgex，w〜999〜chem。 res。毒素。 12,917-923]。我们调查了AP位点与邻居的较小幅度不稳定是嘌呤对嘧啶邻居的一般影响。与相应的控制双工相比，双工稳定性通过掺入与四个碱中的任何一个相对的AP位点（x）而显着降低。然而，对于含有AP位点的T，A或C的双链体，用嘌呤替换与嘌呤的对称双嘧啶碱基导致较小的稳定效果。与嘧啶邻氏植物相比，AP位点对称的AP位点的对称双胞位点的平均稳定效应为3.2 0℃（ATM）和1.3kcab'mol（AAG037）。相反，差距对降低或消除了邻居的差异效果。使用无限制的分子动力学，显示用于含有AP位点与AP位点相对的双链体，围绕AP位点的双链体围绕所述病变位点曲率较大的曲率大小。与侧翼嘧啶相比，侧翼AP位点侧翼的嘌呤倾向于朝向彼此移位，产生重叠。这表明与具有TTXTT和CCXCC序列的那些相比，这表明可以是观察到与AXAXAA和GGXGG中枢序列相比观察到与AXAXA和GGXGG中枢序列的较小热力学稳定化的原因。这项工作表明，对于AP网站，GC含量不是双相稳定性的唯一决定因素，而是通过嘌呤或嘧啶是否侧翼的方法影响更多的方法。

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  • 来源
    《Biochemistry》 |2001年第13期|共10页
  • 作者

    Janos Sagi; Anton B.Guliaev; B.Singer;

  • 作者单位

    Donner Laobraotry Life Sciences Division Lawrence Berkeley National Laboraotry Unviersity of California Berkeley California 94720;

    Donner Laobraotry Life Sciences Division Lawrence Berkeley National Laboraotry Unviersity of California Berkeley California 94720;

    Donner Laobraotry Life Sciences Division Lawrence Berkeley National Laboraotry Unviersity of California Berkeley California 94720;

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  • 正文语种 eng
  • 中图分类 生物化学;
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