Antoniali Giulia, Malfatti Matilde Clarissa, Tell Gianluca
Laboratory of Molecular Biology and DNA repair, Department of Medicine University of Udine, 33100 Udine, Italy.
Laboratory of Molecular Biology and DNA repair, Department of Medicine University of Udine, 33100 Udine, Italy.
DNA Repair (Amst). 2017 Aug;56:65-74. doi: 10.1016/j.dnarep.2017.06.008. Epub 2017 Jun 9.
The Base Excision Repair (BER) pathway, initially studied as a mere DNA repair pathway, has been later found to be implicated in the expression of cancer related genes in human. For several years, this intricate involvement in apparently different processes represented a mystery, which we now are starting to unveil. The BER handles simple alkylation and oxidative lesions arising from both endogenous and exogenous sources, including cancer therapy agents. Surprisingly, BER pathway involvement in transcriptional regulation, immunoglobulin variability and switch recombination, RNA metabolism and nucleolar function is astonishingly consolidating. An emerging evidence in tumor biology is that RNA processing pathways participate in DNA Damage Response (DDR) and that defects in these regulatory connections are associated with genomic instability of cancers. In fact, many BER proteins are associated with those involved in RNA metabolism, ncRNA processing and transcriptional regulation, including within the nucleolus, proving a substantial role of the interactome network in determining their non-canonical functions in tumor cells. Maybe these new insights of BER enzymes, along with their emerging function in RNA-decay, may explain BER essential role in tumor development and chemoresistance and may explain the long-time mystery. Here, we would like to summarize different roles of BER pathway in human cells. First, we will give a short description of the classical BER pathway, which has been covered in detail in recent reviews. We will then outline potential new roles of BER in gene expression and RNA metabolism. Although recent works have provided tremendous amount of data in this field, there are still lot of open questions.
碱基切除修复（BER）途径最初仅作为一种DNA修复途径进行研究，后来发现它与人类癌症相关基因的表达有关。几年来，这种在明显不同过程中的复杂参与一直是个谜，而我们现在正开始揭开这个谜团。BER处理由内源性和外源性来源（包括癌症治疗药物）产生的简单烷基化和氧化损伤。令人惊讶的是，BER途径在转录调控、免疫球蛋白变异性和转换重组、RNA代谢和核仁功能中的参与正日益得到证实。肿瘤生物学中一个新出现的证据是，RNA加工途径参与DNA损伤反应（DDR），并且这些调控联系中的缺陷与癌症的基因组不稳定性有关。事实上，许多BER蛋白与参与RNA代谢、非编码RNA加工和转录调控的蛋白相关，包括在核仁内，这证明了相互作用组网络在确定它们在肿瘤细胞中的非经典功能方面的重要作用。也许BER酶的这些新见解，以及它们在RNA衰变中出现的功能，可以解释BER在肿瘤发展和化疗耐药性中的重要作用，并可以解释这个长期存在的谜团。在这里，我们将总结BER途径在人类细胞中的不同作用。首先，我们将简要描述经典的BER途径，最近的综述中已对此进行了详细介绍。然后，我们将概述BER在基因表达和RNA代谢中的潜在新作用。尽管最近的研究在这个领域提供了大量数据，但仍然有许多悬而未决的问题。
