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Significance of base excision repair to human health
International Review of Cell and Molecular Biology Pub Date : 2021-06-17 , DOI: 10.1016/bs.ircmb.2021.05.002
Shengyuan Zhao 1 , Serkalem Tadesse 1 , Dawit Kidane 1
Affiliation  

Oxidative and alkylating DNA damage occurs under normal physiological conditions and exogenous exposure to DNA damaging agents. To counteract DNA base damage, cells have evolved several defense mechanisms that act at different levels to prevent or repair DNA base damage. Cells combat genomic lesions like these including base modifications, abasic sites, as well as single-strand breaks, via the base excision repair (BER) pathway. In general, the core BER process involves well-coordinated five-step reactions to correct DNA base damage. In this review, we will uncover the current understanding of BER mechanisms to maintain genomic stability and the biological consequences of its failure due to repair gene mutations. The malfunction of BER can often lead to BER intermediate accumulation, which is genotoxic and can lead to different types of human disease. Finally, we will address the use of BER intermediates for targeted cancer therapy.



中文翻译:

碱基切除修复对人体健康的意义

氧化和烷基化 DNA 损伤发生在正常生理条件和外源暴露于 DNA 损伤剂下。为了对抗 DNA 碱基损伤,细胞已经进化出几种防御机制,它们在不同水平上起作用以防止或修复 DNA 碱基损伤。细胞通过碱基切除修复 (BER) 通路对抗基因组损伤,包括碱基修饰、脱碱基位点以及单链断裂。一般来说,核心 BER 过程包括协调良好的五步反应,以纠正 DNA 碱基损伤。在这篇综述中,我们将揭示目前对维持基因组稳定性的 BER 机制的理解,以及由于修复基因突变而导致其失败的生物学后果。BER的故障往往会导致BER中间积累,它具有遗传毒性,可导致不同类型的人类疾病。最后,我们将讨论 BER 中间体在靶向癌症治疗中的应用。

更新日期:2021-06-17
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