A potential role for protein palmitoylation and zDHHC16 in DNA damage response

BMC Molecular Biology

Research Article

Na Cao¹  Huijuan Liu¹  Ji Wu¹  Baojie Li¹  Yu-Qing Rao²  Jia-Kai Li²  Peiquan Zhao²  Jing Li²  Li Zeng³ 

[1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, 200240, Shanghai, China;Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, 308433, Singapore, Singapore;

关键词: Protein palmitoylation;    DNA damage response;    zDHHC16;   

DOI  :  10.1186/s12867-016-0065-9

 received in 2016-01-01, accepted in 2016-04-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCells 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.ResultsInhibition 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.ConclusionsOur results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation.

【 授权许可】

CC BY   
© Cao et al. 2016