title: USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability.
abstract: Excessive accumulation of DNA damage will generate chromosome stress, leading to various chromosome abnormalities such as chromatin bridge and result in genomic instability. Orchestra procession and regulation of DNA damage repair are vital for keeping genome stability. Despite of the key role of HDAC1/2 in double strand break (DSB) repair, the regulation for their mode of action is less well understood. In this study, we found that deubiquitination enzymes USP19 physically interacts with HDAC1/2 and specifically regulate their K63-linked ubiquitination, which might be crucial for regulation of HDAC1/2 activity in DNA damage repair. Notably, we found that USP19 trans-locate into nucleus upon IR irradiation and is indispensable for normally DNA damage response. In addition, we showed that USP19 play critical role in preventing anaphase bridge formation through regulating DNA damage repair process. Furthermore, the expression level of USP19 is commonly lower or deleted in several types of tumor. These results indicated that USP19 is a key factor in modulating DNA damage repair by targeting HDAC1/2 K63-linked ubiquitination, cells with deletion or decreased expression of USP19 might cause genome instability and even contribute to tumorigenesis.
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Min
authors: M
authors: Wu
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Hai-Qing
authors: HQ
authors: Tu
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Yan
authors: Y
authors: Chang
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Bo
authors: B
authors: Tan
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Guang
authors: G
authors: Wang
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Jie
authors: J
authors: Zhou
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.|Beijing Institute of Biotechnology, Beijing 100071, China.
authors: Li
authors: L
authors: Wang
authors: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors: Rui
authors: R
authors: Mu
authors: State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Institute of BasicMedical Sciences, Beijing 100850, China.
authors: Wei-Na
authors: WN
authors: Zhang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D000072017:Deubiquitinating Enzymes / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D054875:Ubiquitination
chemical_list: D010450:Endopeptidases; C559917:USP19 protein, human; D000072017:Deubiquitinating Enzymes; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: DNA repair; HDAC1/2; USP19; genome stability