Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways.
Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways.
复制标题
DOI：
10.3390/ijms22052698
复制
发表时间：
2021-03-07
影响因子：
5.6
通讯作者：
Geacintov NE
中科院分区：
文献类型：
--
作者：
Shafirovich V;Geacintov NE
碱基和核苷酸切除修复途径(分别为BER和NER)是消除遗传毒性中间体与细胞DNA反应形成的DNA损伤的两种主要机制。一般认为，小的非笨重的氧化产生的DNA碱基修饰通过BER途径移除，而由于化学致癌物或紫外线照射的攻击而产生的DNA螺旋扭曲的大损伤则由NER机制修复。然而，现有的和越来越多的实验证据表明，在人类细胞提取物和完整的人类细胞中，氧化生成的DNA损伤可以通过竞争性的BER和NER途径修复。在这里，我们关注BER和NER通路在切除氧化生成的鸟嘌呤损伤中的相互作用和竞争，这些损伤定位于通过缺口载体技术构建的质粒DNA模板中。这些实验表明，含有某些氧化生成的鸟嘌呤损伤的共价闭合环状DNA质粒(相对于相同但线性化的同一质粒)的NER产量显著增加。从BER蛋白和DNA损伤敏感NER因子XPC-RAD23B与这些损伤的竞争结合的角度，综述和讨论了BER和NER通路之间的相互作用，这些通路可以消除氧化生成的鸟嘌呤损伤。
The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.
登录
查看更多内容
影响因子：
5.6
作者：
Czaja W;Mao P;Smerdon MJ
通讯作者：
Smerdon MJ
影响因子：
15
作者：
Fleming AM;Orendt AM;He Y;Zhu J;Dukor RK;Burrows CJ
通讯作者：
Burrows CJ
影响因子：
1.8
作者：
Fleming, Aaron M.;Alshykhly, Omar;Burrows, Cynthia J.
通讯作者：
Burrows, Cynthia J.
DOI：
10.1016/j.mrfmmm.2003.07.002
发表时间：
2003-10-29
影响因子：
2.3
作者：
Bjelland, S;Seeberg, E
通讯作者：
Seeberg, E
DOI：
10.1039/d0cc04138f
发表时间：
2020-08-25
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Fleming AM;Burrows CJ
通讯作者：
Burrows CJ