Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability
Copyright policy )Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability
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.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.NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.
- University of California, Irvine United States
- Cleveland Clinic United States
- University of California, San Francisco United States
- The University of Texas Health Science Center at San Antonio United States
Cancer Research, Lymphoma, chromatin condensation, protein-kinase, Mitosis, Cell Cycle Proteins, dna-damage response, Protein Serine-Threonine Kinases, ionizing-radiation, aspergillus-nidulans, Polyploidy, Mice, Chromosomal Instability, Animals, family kinase, RC254-282, Mice, Knockout, Contact Inhibition, Research, mitotic progression, kidney-disease, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, atm-deficient mice, Aneuploidy, Mice, Inbred C57BL, Cell Transformation, Neoplastic, NIMA-Related Kinase 1, cell-division, Oncology, Mutation, Molecular Medicine, RNA Interference, Neoplasm Transplantation
Cancer Research, Lymphoma, chromatin condensation, protein-kinase, Mitosis, Cell Cycle Proteins, dna-damage response, Protein Serine-Threonine Kinases, ionizing-radiation, aspergillus-nidulans, Polyploidy, Mice, Chromosomal Instability, Animals, family kinase, RC254-282, Mice, Knockout, Contact Inhibition, Research, mitotic progression, kidney-disease, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, atm-deficient mice, Aneuploidy, Mice, Inbred C57BL, Cell Transformation, Neoplastic, NIMA-Related Kinase 1, cell-division, Oncology, Mutation, Molecular Medicine, RNA Interference, Neoplasm Transplantation
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