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

Yumay Chen, Chi Fen Chen, Huai Chin Chiang, Michelle Pena, Rosaria Polci, Randy L. Wei, Robert A. Edwards, Donna E. Hansel, Phang Lang Chen, Daniel J. Riley

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Article number5
JournalMolecular Cancer
Volume10
DOIs
StatePublished - Jan 10 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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