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

Cao N, Li JK, Rao YQ, Liu H, Wu J, Li B, Zhao P, Zeng L, Li J - BMC Mol. Biol. (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Inhibition of palmitoylation impaired assembly/disassembly of DNA damage foci. Primary MEFs grown on coverslips were pre-treated with 50 μM 2BP for 24 h and then treated with 1 μM Dox for different periods of time. The cells were then fixed and immune-stained for H2AX using Texas-red conjugated secondary antibodies (a). b Averaged number of foci per cell from multiple repeated experiments and multiple cells per experiment. Asterisk denoted significant difference (p < 0.05) between compared groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4862184&req=5

Fig4: Inhibition of palmitoylation impaired assembly/disassembly of DNA damage foci. Primary MEFs grown on coverslips were pre-treated with 50 μM 2BP for 24 h and then treated with 1 μM Dox for different periods of time. The cells were then fixed and immune-stained for H2AX using Texas-red conjugated secondary antibodies (a). b Averaged number of foci per cell from multiple repeated experiments and multiple cells per experiment. Asterisk denoted significant difference (p < 0.05) between compared groups

Mentions: We also looked at the formation of DNA damage foci in the presence of 2BP. In normal MEFs, Dox treatment induced DNA damage foci positive for γH2AX, TopBP1, and Brca1, which are believed to be signal propagation centers as well as DNA repair centers (Fig. 4a, b). In 2BP-treated cells, the number of foci positive for γH2AX was higher than those in controls, especially at 8 and 16 h after Dox treatment. These results suggest that 2BP interferes with the assembly/disassembly of the DNA damage foci or the DNA repair process.Fig. 4


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

Cao N, Li JK, Rao YQ, Liu H, Wu J, Li B, Zhao P, Zeng L, Li J - BMC Mol. Biol. (2016)

Inhibition of palmitoylation impaired assembly/disassembly of DNA damage foci. Primary MEFs grown on coverslips were pre-treated with 50 μM 2BP for 24 h and then treated with 1 μM Dox for different periods of time. The cells were then fixed and immune-stained for H2AX using Texas-red conjugated secondary antibodies (a). b Averaged number of foci per cell from multiple repeated experiments and multiple cells per experiment. Asterisk denoted significant difference (p < 0.05) between compared groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4862184&req=5

Fig4: Inhibition of palmitoylation impaired assembly/disassembly of DNA damage foci. Primary MEFs grown on coverslips were pre-treated with 50 μM 2BP for 24 h and then treated with 1 μM Dox for different periods of time. The cells were then fixed and immune-stained for H2AX using Texas-red conjugated secondary antibodies (a). b Averaged number of foci per cell from multiple repeated experiments and multiple cells per experiment. Asterisk denoted significant difference (p < 0.05) between compared groups
Mentions: We also looked at the formation of DNA damage foci in the presence of 2BP. In normal MEFs, Dox treatment induced DNA damage foci positive for γH2AX, TopBP1, and Brca1, which are believed to be signal propagation centers as well as DNA repair centers (Fig. 4a, b). In 2BP-treated cells, the number of foci positive for γH2AX was higher than those in controls, especially at 8 and 16 h after Dox treatment. These results suggest that 2BP interferes with the assembly/disassembly of the DNA damage foci or the DNA repair process.Fig. 4

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus