The integrity of the genetic information is continuously challenged by numerous genotoxic insults, most frequently in the form of oxidation, alkylation or deamination of the bases that result in DNA damage. These damages compromise the fidelity of the replication, and interfere with the progression and function of the transcription machineries. The DNA damage response (DDR) comprises a series of strategies to deal with DNA damage, including transient transcriptional inhibition, activation of DNA repair pathways and chromatin remodeling. Coordinated control of transcription and DNA repair is required to safeguardi cellular functions and identities. Here, we address the cellular responses to endogenous DNA damage, with a particular focus on the role of DNA glycosylases and the Base Excision Repair (BER) pathway, in conjunction with the DDR factors, in responding to DNA damage during the transcription process. We will also discuss functions of newly identified epigenetic and regulatory marks, such as 5-hydroxymethylcytosine and its oxidative products and 8-oxoguanine, that were previously considered only as DNA damages. In light of these resultsthe classical perception of DNA damage as detrimental for cellular processes are changing. and a picture emerges whereDNA glycosylases act as dynamic regulators of transcription, placing them at the intersection of DNA repair and gene expression modulation.

遗传信息的完整性不断受到众多基因毒性损伤的挑战，最常见的形式是碱基的氧化、烷基化或脱氨基，从而导致 DNA 损伤。这些损害损害了复制的保真度，并干扰了转录机制的进程和功能。DNA 损伤反应 (DDR) 包括一系列处理 DNA 损伤的策略，包括瞬时转录抑制、DNA 修复途径的激活和染色质重塑。需要对转录和 DNA 修复进行协调控制以保护细胞功能和身份。在这里，我们解决了对内源性 DNA 损伤的细胞反应，特别关注 DNA 糖基化酶和碱基切除修复 (BER) 途径的作用，以及 DDR 因子，在转录过程中对 DNA 损伤做出反应。我们还将讨论新发现的表观遗传和调控标记的功能，例如 5-羟甲基胞嘧啶及其氧化产物和 8-氧鸟嘌呤，这些以前仅被认为是 DNA 损伤。鉴于这些结果，DNA 损伤对细胞过程有害的经典认知正在发生变化。并且出现了一幅图，其中 DNA 糖基化酶充当转录的动态调节器，将它们置于 DNA 修复和基因表达调节的交叉点。鉴于这些结果，DNA 损伤对细胞过程有害的经典认知正在发生变化。并且出现了一幅图，其中 DNA 糖基化酶充当转录的动态调节器，将它们置于 DNA 修复和基因表达调节的交叉点。鉴于这些结果，DNA 损伤对细胞过程有害的经典认知正在发生变化。并且出现了一幅图，其中 DNA 糖基化酶充当转录的动态调节器，将它们置于 DNA 修复和基因表达调节的交叉点。