Removal of oxidatively generated DNA damage by overlapping repair pathways.
Removal of oxidatively generated DNA damage by overlapping repair pathways.
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DOI：
10.1016/j.freeradbiomed.2016.10.507
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发表时间：
2017-06
影响因子：
7.4
通讯作者：
Geacintov NE
中科院分区：
文献类型：
--
作者：
Shafirovich V;Geacintov NE
通常认为，哺乳动物核苷酸切除修复途径去除DNA螺旋扭曲的大体积DNA损伤，而小的非大体积损伤通过碱基切除修复（BER）修复。然而，最近的工作表明，氧化产生的鸟嘌呤氧化产物、螺亚氨基二乙内酰脲（Sp）、5-胍基乙内酰脲（Gh）和某些链内交联损伤是NER和BER途径的良好底物，它们在人体细胞中相互竞争提取物。已知鸟嘌呤被过氧亚硝酸盐氧化生成5-胍基-4-硝基咪唑（NIm），其结构类似于Gh，除了NIm中的4-硝基被Gh中的酮基取代。然而，与Gh不同，NIm是BER的优良底物，但不是NER的底物。这些和其他相关的结果在这篇文章中进行了审查和讨论。
It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh. However, unlike Gh, NIm is an excellent substrate of BER, but not of NER. These and other related results are reviewed and discussed in this article.