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

作者：Cao, Na; Li, Jia-Kai; Rao, Yu-Qing; Liu, Huijuan; Wu, Ji; Li, Baojie; Zhao, Peiquan; Zeng, Li^*; Li, Jing

来源：BMC Molecular Biology, 2016, 17(1): 12.

DOI：10.1186/s12867-016-0065-9

• Protein palmitoylation
• DNA damage response
• zDHHC16

Background: 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. @@@ Results: 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. @@@ Conclusions: 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.

• 出版日期2016-5-10
• 单位上海交通大学