HDAC3 Is Required for XPC Recruitment and Nucleotide Excision Repair of DNA Damage Induced by UV Irradiation
HDAC3 Is Required for XPC Recruitment and Nucleotide Excision Repair of DNA Damage Induced by UV Irradiation
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DOI：
10.1158/1541-7786.mcr-20-0214
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发表时间：
2020-09-01
影响因子：
5.2
通讯作者：
Kitagawa, Masatoshi
中科院分区：
文献类型：
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作者：
Nishimoto, Koji;Niida, Hiroyuki;Kitagawa, Masatoshi
最近的研究表明，组蛋白的赖氨酸乙酰化通过松弛染色质结构，促进修复因子的募集，对于核苷酸切除修复 (NER) 至关重要。然而，很少有研究关注组蛋白脱乙酰酶 (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 脱乙酰化。 HDAC3 的耗尽会导致环丁烯嘧啶二聚体切除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 RNA 合成没有恢复，这表明 HDAC3 是全局基因组 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 XPC 在 DNA 损伤位点积累的延迟之外，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 的去乙酰化有助于 XPC 募集至 DNA 损伤，从而促进整体基因组 NER。
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.