UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Hanqing He, Jiajia Wang, Ting Liu
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.

Graphical abstract

Teaser

He et al. find that the RPA1 protein becomes acetylated at lysine 163 in response to UV irradiation. Such acetylation specifically enhances interaction between RPA1 and the key NER protein XPA and promotes XPA retention at DNA damage sites. These findings suggest that RPA1 acetylation is a unique NER-related event.


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