He Hanqing, Wang Jiajia, Liu Ting
Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Cell Rep. 2017 Aug 29;20(9):2010-2025. doi: 10.1016/j.celrep.2017.08.016.
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 acetyltransferases 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 hypersensitive to UV irradiation. Our data suggest that the acetylation status of RPA1 played a crucial role in repair of DNA damage via NER.
复制蛋白A（RPA）是一种多功能单链DNA结合蛋白复合物，在DNA复制和损伤应答中起关键作用。在此，我们发现RPA的70 kDa亚基（RPA1）在赖氨酸163处被乙酰转移酶GCN5和PCAF乙酰化，且这种乙酰化主要通过去乙酰化酶HDAC6的作用而逆转。紫外线照射促进HDAC6的细胞质转位，从而破坏HDAC6与RPA1的相互作用并增加RPA1的乙酰化。RPA1乙酰化位点的突变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高度敏感。我们的数据表明，RPA1的乙酰化状态在通过NER修复DNA损伤中起关键作用。
