Deng Q, Holler CJ, Taylor G, Hudson KF, Watkins W, Gearing M, Ito D, Murray ME, Dickson DW, Seyfried NT, Kukar T.
FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA damage.
J Neurosci. 2014 Jun 4;34(23):7802-13.
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This is an interesting paper. I think the DNA damage response the authors report happens in a transient process, but prolonged activation of this DNA damage response may do more harm to cells. I like the aspect of phosphorylation of FAK by DNA-PK. We previously noted that FAK could be phosphorylated because it sometimes appeared as doublets on western blots, but we did not look into this.
While the authors show cytoplasmic translocation of FUS following phosphorylation, there is still lot of nuclear FUS remaining (see Fig 7D). Also, under chronic stress, nuclear integrity may be compromised, which may also explain cytoplasmic translocation of FUS.
I like the authors' speculation that "FUS may be initially recruited to sites of DNA damage, where it is phosphorylated by DNA-PK, leading to release from the DNA lesion and export to the cytoplasm of FUS after DNA damage."
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