title: A potential role for protein palmitoylation and zDHHC16 in DNA damage response.
abstract: Cells respond to DNA damage by activating the phosphatidylinositol-3 kinase-related kinases, p53 and other pathways to promote cell cycle arrest, apoptosis, and/or DNA repair. Here we report that protein palmitoylation, a modification carried out by protein acyltransferases with zinc-finger and Asp-His-His-Cys domains (zDHHC), is required for proper DNA damage responses.
  
  
  
  Inhibition of protein palmitoylation compromised DNA damage-induced activation of Atm, induction and activation of p53, cell cycle arrest at G2/M phase, and DNA damage foci assembly/disassembly in primary mouse embryonic fibroblasts. Furthermore, knockout of zDHHC16, a palmitoyltransferase gene identified as an interacting protein for c-Abl, a non-receptor tyrosine kinase involved in DNA damage response, reproduced most of the defects in DNA damage responses produced by the inhibition of protein palmitoylation.
  
  
  
  Our results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Na
authors.initials: N
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jia-Kai
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Rao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Peiquan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, 308433, Singapore. li_zeng@nni.com.sg.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lj_xinhua@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000217:Acyltransferases; D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D054878:Lipoylation; D008810:Mice, Inbred C57BL; D060066:Protein Interaction Maps; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016159:Tumor Suppressor Protein p53; D000217:Acyltransferases; C464939:Zdhhc16 protein, mouse; D016315:Proto-Oncogene Proteins c-abl; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse
keywords: DNA damage response; Protein palmitoylation; zDHHC16