title: Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability.
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.
  
  
  CONCLUSIONS
  NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California at Irvine, 1130 Gross Hall, Irvine, CA 92697, USA. yumayc@uci.edu
authors.forename: Yumay
authors.initials: Y
authors.lastname: Chen
authors.forename: Chi-Fen
authors.initials: CF
authors.lastname: Chen
authors.forename: Huai-Chin
authors.initials: HC
authors.lastname: Chiang
authors.forename: Michelle
authors.initials: M
authors.lastname: Pena
authors.forename: Rosaria
authors.initials: R
authors.lastname: Polci
authors.forename: Randy L
authors.initials: RL
authors.lastname: Wei
authors.forename: Robert A
authors.initials: RA
authors.lastname: Edwards
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.forename: Phang-Lang
authors.initials: PL
authors.lastname: Chen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Riley
mesh_terms: D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D043171:Chromosomal Instability; D003260:Contact Inhibition; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis; D009154:Mutation; D000072380:NIMA-Related Kinase 1; D009368:Neoplasm Transplantation; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D018797:Cell Cycle Proteins; D000072380:NIMA-Related Kinase 1; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases