Nucleotide excision repair (NER) is the main pathway to repair bulky DNA damages including pyrimidine dimers, and the genetic dysregulation of NER associated proteins is well known to cause diseases such as cancer and neurological disorder. Other than the genetic defects, ‘external factors’ such as oxidative stress and environmental chemicals also affect NER. In this study, we examined the impact of extracellular pH on NER. We prepared the culture media, whose pH values are 8.4 (normal condition), 7.6, 6.6 and 6.2 under atmospheric CO₂ conditions. Human keratinocytes, HaCaT, slightly died after 48 h incubation in DMEM at pH 8.4, 7.6 and 6.6, while in pH 6.2 condition, marked cell death was induced. UV-induced pyrimidine dimers, pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) and cyclobutane pyrimidine dimers (CPDs), were effectively repaired at 60 min and 24 h, respectively, which were remarkably inhibited at pH 6.6 and 6.2. The associated repair molecule, TFIIH, was accumulated to the damaged sites 5 min after UVC irradiation in all pH conditions, but the release was delayed as the pH got lower. Furthermore, accumulation of XPG at 5 min was delayed at pH 6.2 and 6.6, and the release at 60 min was completely suppressed. At the low pH, the DNA synthesis at the gaps created by incision of oligonucleotides containing pyrimidine dimers was significantly delayed. In this study, we found that the low extracellular pH inhibited NER pathway. This might partially contribute to carcinogenesis in inflamed tissues, which exhibit acidic pH.

核苷酸切除修复 (NER) 是修复包括嘧啶二聚体在内的大量 DNA 损伤的主要途径，众所周知，NER 相关蛋白的遗传失调会导致癌症和神经系统疾病等疾病。除了遗传缺陷，氧化应激和环境化学物质等“外部因素”也会影响 NER。在这项研究中，我们检查了细胞外 pH 值对 NER 的影响。我们在大气 CO ₂下制备了 pH 值为 8.4（正常条件）、7.6、6.6 和 6.2 的培养基状况。在 pH 8.4、7.6 和 6.6 的 DMEM 中孵育 48 小时后，人角质形成细胞 HaCaT 轻微死亡，而在 pH 6.2 条件下，会诱导明显的细胞死亡。紫外线诱导的嘧啶二聚体、嘧啶 (6-4) 嘧啶酮光产物 (6-4PPs) 和环丁烷嘧啶二聚体 (CPD) 分别在 60 分钟和 24 小时得到有效修复，在 pH 6.6 和 6.2 时受到显着抑制。在所有 pH 条件下，UVC 照射 5 分钟后，相关的修复分子 TFIIH 会积累到受损部位，但随着 pH 值降低，释放会延迟。此外，在 pH 6.2 和 6.6 时，XPG 在 5 分钟时的积累被延迟，并且在 60 分钟时的释放被完全抑制。在低 pH 值下，切割含有嘧啶二聚体的寡核苷酸产生的间隙处的 DNA 合成显着延迟。在这项研究中，我们发现低细胞外 pH 值抑制了 NER 通路。这可能部分导致发炎组织的致癌作用，这些组织表现出酸性 pH 值。