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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-016-0065-9) contains supplementary material, which is available to authorized users.

Assessment of Radiation Induced DNA Damage in Human Peripheral Blood Lymphocytes Using COMET Assay

“…All the cancer patients and medical workers showed DNA damage but the extent of damage was significantly higher among the cancer patients. Similar findings have been reported by many earlier studies [21,[24][25][26] except one study in which the authors have reported negative results [27] . The comet tail length was surprisingly very low in both, treated (radiotherapy) and untreated cancer patients (ranging between 0.91 to 3.76).…”

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

“…Its name Ablphilin stems from its ability to interact with the non-receptor tyrosine kinase c-Abl at the ER surface ( Li et al, 2002 ). ZDHHC16/Aph2 is essential for embryonic and postnatal survival, eye and heart development in mice ( Zhou et al, 2015 ), for the proliferation of neural stem cells, where it is involved in the activation of the FGF/erk pathways ( Shi et al, 2016 ) and was reported to play a role in DNA damage response ( Cao et al, 2016 ). Our findings raise the possibility that some of these effects may involve ZDHHC6.…”

Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

“…However, the functional consequences for most targets of S- acylation remain to be determined. Interestingly, chemical inhibition of protein S -palmitoylation in mammalian cells led to a muted DNA-damage response 60 . Here, we uncover a role for protein S- acylation in DSB repair pathway choice.…”