title: Autophagy substrate SQSTM1/p62 regulates chromatin ubiquitination during the DNA damage response.
abstract: The importance of autophagy in the DNA damage repair process is clear; however, the detailed molecular mechanism is still largely unknown. Here we found that DNA damage-induced histone H2A ubiquitination is suppressed in autophagy-deficient cells in a SQSTM1/p62 dependent manner. SQSTM1 binds and inhibits E3 ligase RNF168s activity, which is essential for H2A ubiquitination. As a result, several important factors for DNA repair cannot be recruited to the sites of DNA double-strand breaks (DSBs) in autophagy-deficient cells, leading to diminished DNA repair and increased sensitivity of cells to radiation.
authors: a Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function , Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, Peking University Health Science Center , Beijing , China.
authors: Yanan
authors: Y
authors: Wang
authors: a Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function , Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, Peking University Health Science Center , Beijing , China.|b Center for Life Sciences, Peking-Tsinghua University , Beijing , China.|c School of Medicine, Shenzhen University , Shenzhen , China.
authors: Wei-Guo
authors: WG
authors: Zhu
authors: a Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function , Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, Peking University Health Science Center , Beijing , China.
authors: Ying
authors: Y
authors: Zhao
mesh_terms: D001343:Autophagy; D002470:Cell Survival; D002843:Chromatin / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D008024:Ligands; D010957:Plasmids; D000071456:Sequestosome-1 Protein / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D008024:Ligands; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: DNA damage; RNF168; autophagy; histone ubiquitination; p62