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- Title
Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability.
- Authors
Yumay Chen; Chi-Fen Chen; Huai-Chin Chiang; Pena, Michelle; Polci, Rosaria; Wei, Randy L.; Edwards, Robert A.; Hansel, Donna E.; Phang-Lang Chen; Riley, Daniel J.
- 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 anchorageindependent 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.
- Subjects
DNA damage; PROTEIN kinases; LYMPHOPROLIFERATIVE disorders; GENETIC mutation; BIOCHEMICAL genetics
- Publication
Molecular Cancer, 2011, Vol 10, Issue 1, p1
- ISSN
1476-4598
- Publication type
Article
- DOI
10.1186/1476-4598-10-5