title: iTRAQ-based chromatin proteomic screen reveals CHD4-dependent recruitment of MBD2 to sites of DNA damage.
abstract: Many DNA repair proteins can be recruited to DNA damage sites upon genotoxic stress. In order to search potential DNA repair proteins involved in cellular response to mitomycin C treatment, we utilized a quantitative proteome to uncover proteins that manifest differentially enrichment in the chromatin fraction after DNA damage. 397 proteins were identified, among which many factors were shown to be involved in chromatin modification and DNA repair by GO analysis. Specifically, methyl-CpG-binding domain protein 2 (MBD2) is revealed to be recruited to DNA damage sites after laser microirradiation, which was mediated through MBD domain and MBD2 C-terminus. Additionally, the recruitment of MBD2 is dependent on poly (ADP-ribose) and chromodomain helicase DNA-binding protein 4 (CHD4). Moreover, knockdown of MBD2 by CRISPR-Cas9 technique results in MMC sensitivity in mammalian cells.
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
authors.forename: Yeran
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Shen
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Tie-Shan
authors.initials: TS
authors.lastname: Tang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address: guocx@big.ac.cn.
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D001665:Binding Sites; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D010449:Peptide Mapping / Q000379:methods*; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism*; D011829:Radiation Dosage; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C489325:MBD2 protein, human; D020543:Proteome; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: CHD4; Chromatin fraction; DNA damage response; MBD2; PAR; iTRAQ