每天在细胞中发生超过70,000个DNA损伤,无法正确修复它们会导致突变并破坏基因组的稳定性,导致致癌。碱基切除修复(BER)途径对于通过修复小碱基病变来维持基因组完整性至关重要,abasic位点和单链断裂。单功能和双功能的糖基化酶通过识别和切除特定的碱基病变来启动BER的第一步,然后是DNA末端处理,间隙填充,最后是尼克·密封。Nei样2(NEIL2)酶是BER中的关键双功能DNA糖基化酶,可优先从单链中切除胞嘧啶氧化产物和无碱基位点,双链,和气泡结构的DNA.NEIL2被认为在几种细胞功能中具有重要作用,包括基因组维护,参与主动去甲基化,和调节免疫反应。在文献中已经报道了具有改变的表达和酶活性的NEIL2的几种种系和体细胞变体将它们与癌症联系起来。在这次审查中,我们概述了NEIL2细胞功能,并总结了NEIL2变异体及其与癌症的关系的最新发现.本文受版权保护。保留所有权利。
Over 70,000 DNA lesions occur in the cell every day, and the inability to properly repair them can lead to mutations and destabilize the genome, resulting in carcinogenesis. The base excision repair (BER) pathway is critical for maintaining genomic integrity by repairing small base lesions, abasic sites and single-stranded breaks. Monofunctional and bifunctional glycosylases initiate the first step of BER by recognizing and excising specific base lesions, followed by DNA end processing, gap filling, and finally nick sealing. The Nei-like 2 (NEIL2) enzyme is a critical bifunctional DNA glycosylase in BER that preferentially excises cytosine oxidation products and abasic sites from single-stranded, double-stranded, and bubble-structured DNA. NEIL2 has been implicated to have important roles in several cellular functions, including genome maintenance, participation in active demethylation, and modulation of the immune response. Several germline and somatic variants of NEIL2 with altered expression and enzymatic activity have been reported in the literature linking them to cancers. In this review, we provide an overview of NEIL2 cellular functions and summarize current findings on NEIL2 variants and their relationship to cancer.