Recent studies have demonstrated that lysine acetylation of histones is crucial for nucleotide excision repair (NER) by relaxing the chromatin structure, which facilitates the recruitment of repair factors. However, few studies have focused on the contribution of histone deacetylases (HDAC) to NER. Here, we found that histone H3 Lys14 (H3K14) was deacetylated by HDAC3 after UV irradiation. Depletion of HDAC3 caused defects in cyclobutene pyrimidine dimer excision and sensitized cells to UV irradiation. HDAC3-depleted cells had impaired unscheduled DNA synthesis, but not recovery of RNA synthesis, which indicates that HDAC3 was required for global genome NER. Moreover, xeroderma pigmentosum, complementation group C (XPC) accumulation at the local UV-irradiated area was attenuated in HDAC3-depleted cells. In addition to the delay of XPC accumulation at DNA damage sites, XPC ubiquitylation was inhibited in HDAC3-depleted cells. These results suggest that the deacetylation of histone H3K14 by HDAC3 after UV irradiation contributes to XPC recruitment to DNA lesions to promote global genome NER. Implications: Involvement of histone deacetylation for XPC accumulation after UV irradiation indicates conversion of chromatin structure is essential for nucleotide excision repair in human cancer cells.

中文翻译：

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XPC 募集和核苷酸切除修复紫外线照射引起的 DNA 损伤需要 HDAC3

最近的研究表明，组蛋白的赖氨酸乙酰化通过放松染色质结构对核苷酸切除修复 (NER) 至关重要，这有助于修复因子的募集。然而，很少有研究关注组蛋白去乙酰化酶 (HDAC) 对 NER 的贡献。在这里，我们发现组蛋白 H3 Lys14 (H3K14) 在紫外线照射后被 HDAC3 去乙酰化。HDAC3 的消耗导致环丁烯嘧啶二聚体切除的缺陷并使细胞对紫外线照射敏感。HDAC3 耗尽的细胞损害了计划外的 DNA 合成，但未恢复 RNA 合成，这表明 HDAC3 是全球基因组 NER 所必需的。此外，在 HDAC3 耗尽的细胞中，色素性干皮病、互补组 C (XPC) 在局部紫外线照射区域的积累减弱。除了在 DNA 损伤位点延迟 XPC 积累外，XPC 泛素化在 HDAC3 耗尽的细胞中也受到抑制。这些结果表明，紫外线照射后 HDAC3 对组蛋白 H3K14 的脱乙酰作用有助于 XPC 募集到 DNA 病变以促进全球基因组 NER。意义：紫外线照射后组蛋白去乙酰化参与 XPC 积累表明染色质结构的转化对于人类癌细胞中的核苷酸切除修复至关重要。