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首页> 外文期刊>Biochemistry >Interaction of DNA containing Fapy center dot dA or its C-nucleoside analogues with base excision repair enzymes. Implications for mutagenesis and enzyme inhibition
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Interaction of DNA containing Fapy center dot dA or its C-nucleoside analogues with base excision repair enzymes. Implications for mutagenesis and enzyme inhibition

机译：含有Fapy中心点dA的DNA或其C-核苷类似物与碱基切除修复酶的相互作用。对诱变和酶抑制的影响

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Fapy.dA is produced in DNA as a result of oxidative stress. Recently, this lesion and its C-nucleoside analogues were incorporated in chemically synthesized oligonucleotides at defined sites. The interaction of DNA containing Fapy.dA or nonhydrolyzable analogues with Fpg and MutY is described. Fpg efficiently excises Fapy.dA (K-m = 1.2 nM, k(cat) = 0.12 min(-1)) opposite T. The lesion is removed as efficiently from duplexes containing Fapy.dA:dA or Fapy.dA:dG base pairs. Multiple turnovers are observed for the repair of Fapy.dA mispairs in a short period of time, indicating that the enzyme does not remain bound to the product duplex. MutY does not incise dA from a duplex containing this nucleotide opposite Fapy.dA, nor does it exhibit an increased level of binding compared to DNA composed solely of native base pairs. MutY also does not incise Fapy.dA when the lesion is opposite dG. These data suggest that Fapy.dA could be deleterious to the genome. Fpg strongly binds duplexes containing the beta-C-nucleoside analogue of Fapy.dA (beta-C-Fapy.dA) opposite all native nucleotides (K-D < 27 nM), as well as the alpha-C-nucleoside (alpha-C-Fapy.dA) opposite dC (K-D = 7.1 +/- 1.5 nM). A duplex containing a beta-C-Fapy.dA:T base pair is an effective inhibitor (K-I = 3.5 +/- 0.3 nM) of repair of Fapy.dA by Fpg, suggesting the C-nucleoside may have useful therapeutic properties. [References: 38]
机译：Fapy.dA是由于氧化应激而在DNA中产生的。最近，该病灶及其C-核苷类似物在确定的位点被掺入化学合成的寡核苷酸中。描述了含有Fapy.dA或不可水解类似物的DNA与Fpg和MutY的相互作用。 Fpg有效地切除了与T相对的Fapy.dA（K-m = 1.2 nM，k（cat）= 0.12 min（-1））。从包含Fapy.dA：dA或Fapy.dA：dG碱基对的双链体中有效去除了病变。 Fapy.dA错配的修复在短时间内观察到多次翻转，表明该酶未保持与产物双链体的结合。与仅由天然碱基对组成的DNA相比，MutY不会从含有与Fapy.dA相对的该核苷酸的双链体切出dA，也不会表现出增加的结合水平。当病变与dG相对时，MutY也不会切割Fapy.dA。这些数据表明，Fapy.dA可能对基因组有害。 Fpg与含有与所有天然核苷酸（KD <27 nM）相对的Fapy.dA（β-C-Fapy.dA）的β-C-核苷类似物和α-C-核苷（α-C- Fapy.dA）与dC相反（KD = 7.1 +/- 1.5 nM）。含有β-C-Fapy.dA：T碱基对的双链体是Fpg修复Fapy.dA的有效抑制剂（K-1 = 3.5 +/- 0.3 nM），表明C-核苷可能具有有用的治疗特性。 [参考：38]

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