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NIMA-Related Protein Kinase 1 Is Involved Early in the Ionizing Radiation-Induced DNA Damage Response

¹ Department of Medicine, Division of Nephrology and ² Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas; ³ Department of Clinical Science, Division of Nephrology, Policlinico Umberto I, University "La Sapienza," Rome, Italy; and ⁴ Research Division, South Texas Veterans Health Care System, San Antonio, Texas

Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with -H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway.

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