UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair
UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair
复制标题
紫外线诱导的 RPA1 乙酰化促进核苷酸切除修复
DOI：
10.1016/j.celrep.2017.08.016
复制
发表时间：
2017-08-29
期刊：
影响因子：
8.8
通讯作者：
Liu, Ting
中科院分区：
文献类型：
--
作者：
He, Hanqing;Wang, Jiajia;Liu, Ting
复制蛋白 A (RPA) 是一种多功能、单链 DNA 结合蛋白复合物，在 DNA 复制和损伤反应中发挥着关键作用。在此，我们证明 RPA (RPA1) 的 70 kDa 亚基在赖氨酸 163 上被乙酰转移酶 GCN5 和 PCAF 乙酰化，并且这种乙酰化主要通过脱乙酰酶 HDAC6 的作用逆转。紫外线照射促进 HDAC6 的细胞质易位，从而破坏 HDAC6 与 RPA1 的相互作用并增加 RPA1 乙酰化。 RPA1 乙酰化位点的突变会特异性损害该蛋白与关键核苷酸切除修复 (NER) 蛋白 XPA 相互作用的能力，减少 XPA 在紫外线引起的 DNA 损伤位点的保留，损害 NER，并使细胞对紫外线照射过度敏感。我们的数据表明 RPA1 的乙酰化状态在通过 NER 修复 DNA 损伤中发挥着至关重要的作用。
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltrans-ferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation. Mutation of the acetylation site of RPA1 specifically impairs the ability of the protein to interact with the key nucleotide excision repair (NER) protein XPA, reduces XPA retention at sites of DNA damage caused by UV, compromises NER, and renders the cell hyper-sensitive to UV irradiation. Our data suggest that the acetylation status of RPA1 played a crucial role in repair of DNA damage via NER.