Robert Hromas, Austin Kirby, Andrew Carrillo, Aruna Jasiwal, Kimi Kong, Manh Tien Tran, Dominic Arris, Elizabeth A. Williamson
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The DNA Repair Component EEPD1 Regulates Actin Polymerization
Endonuclease exonuclease phosphatase domain-containing protein 1 (EEPD1) is a DNase1 superfamily member that has DNA endonuclease activity. It plays a critical role in multiple DNA repair processes such as oxidative damage repair and stressed replication fork repair. Interestingly, EEPD1 is myristoylated and palmitoylated near its amino terminus in response to high levels of cholesterol, and this localizes EEPD1 protein to the inner cell membrane. Surprisingly, we found that EEPD1 promotes cortical branching actin polymerization and proper lamellipodia formation and is necessary for subsequent cell migration. EEPD1's enhancement of actin polymerization partially required its myristoylation and palmitoylation. EEPD1 depletion also resulted in marked abnormalities in nuclear morphology. Loss of EEPD1 resulted in loss of phosphorylation of SRC, RAC1, cortactin, and profilin, which are essential steps in signaling for actin polymerization. Loss of EEPD1 lowered SRC kinase activity, which would harm actin polymerization. In summary, EEPD1 is a novel, positive regulator of the signaling pathway for actin polymerization, linking actin regulation to nuclear morphology and DNA repair.
期刊介绍:
The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms.
This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.