Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

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Abstract

Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability. © 2011 Chen et al; licensee BioMed Central Ltd.

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Chen, Y., Chen, C. F., Chiang, H. C., Pena, M., Polci, R., Wei, R. L., … Riley, D. J. (2011). Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability. Molecular Cancer, 10. https://doi.org/10.1186/1476-4598-10-5

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